Download Biochemistry

The First Page of Teaching Plan
No.
course
Biochemistry
specialty
Clinic medicine
class
2015-2
lecturer
Yan Chen
period
8
students’
level
undergraduate
professiona
l title
Biochemistry associate professor
time of
writing
2016.11
chapter
RNA Biological Synthesis----Transcription
time of
using
2016-2017（1）
objectives
and
requiremen
ts
1. The template, enzymes and processing of RNA biological synthesis. (First class)
2. Post-transcriptional modification in eukaryotes. (Second class)
Keys:Template
keys and
difficulties
and
RNA
polymerase;processing
of
RNA
biological
synthesis;
Post-transcriptional modification in eukaryotes(mRNA)
Difficulties: initiation, and termination in prokaryotes
updated
informatio
n
no
review the content last class(20min); the template and enzymes (80min); processing of RNA
arrangeme
nt
biological synthesis(100min); Post-transcriptional modification in eukaryotes(50min).
ribozyme(20min); Reverse Transcription(20min); The processes differ in DNA and RNA
synthesis(35min); discuss and summarize(35min).
teaching
methods
Using CAI to explain, enlightening method
Lippincott’s illustrated review :Biochemistry Pamela C. Champe
wilkins 2009
books and
references
teachers’
group
discussion
about the
plan
Biochemistry
the second edition
High Education Press 2002
author: Reginald H. Garrett, Charles M. Grisham
According to learn the RNA polymerase, then to emphasized the classification and its function
of RNA polymerase in eukaryotes. The processing of RNA biological synthesis in prokaryotes
should be lectured clearly.
Agreement.
comments
from the
department
Lippincott’s willam &
Sign name:
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Lesson plan for page
Chapter 10
RNA Biosynthesis ----Transcription
I.Teaching Goals
It is based on a mastery of transcription in prokaryotes, then to be familiar with
RNA processing in eukaryotes.
II.Teaching Demands
1.Master the template, enzymes and transcription process in prokaryotes.
2.Familiar with RNA processing in eukaryotes.
3.Understand initiation and termination of transcription in eukaryotes.
III.Teaching Contents
1. The concept of transcription and the concept of RNA replication
2.Template and enzymes
The template for RNA synthesis and RNA polymerase subunits of
prokaryotes. The function of RNA polymerase subunits in prokaryotes.
Classification and function of RNA polymerase in eukaryotes. The inhibitor of
RNA polymerase.
3.The process of transcription
Three phases of transcription: initiation, elongation and termination in
prokaryotes. The transcription of initiation and termination in eukaryotes
(self-study).
4.Posttranscriptional processing of RNAs in eukaryotes
The posttranscriptional processing of mRNA, tRNA and rRNA.
IV. Class Hour
8 hours
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Lesson plan for page
Chapter 10 RNA synthesis
REVIEW
According to what has been called the central dogma of molecular genetics, the
function of DNA is to store information and pass it on to RNA, while the function
of RNA is to read, decode and use the information received from DNA to make
proteins.
Reverse Transcription
Three fundamental processes take place in the transfer and use of genetic information:
Replication is the process by which a replica, or identical copy, of DNA is made.
Replication occurs every time a cell divides so that information can be preserved and
handed down to offspring. This is similar to making a copy of a file onto a disk so
you can take that file to a different computer.
Transcription is the process by which the genetic messages contained in DNA are
"read" or transcribed. The product of transcription, known as messenger RNA
(mRNA), leaves the cell nucleus and carries the message to the sites of protein
synthesis. (This tutorial explains later why this step is necessary in organisms with a
nucleus!)
Translation is the process by which the genetic messages carried by mRNA are
decoded and used to build proteins.
What is RNA?
RNA is structurally similar to DNA.
Both nucleic acids are sugar-phosphate polymers and both have nitrogen bases
attached to the sugars of the backbone- but there are several important differences.
1.They differ in composition:
(1)The sugar in RNA is ribose, not the deoxyribose in DNA (as we previously
learned).
(2)The base uracil is present in RNA instead of thymine.
2.They also differ in size and structure:
(1)RNA molecules are smaller (shorter) than DNA molecules.
(2)RNA is single-stranded, not double-stranded like DNA.
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3.Another difference between RNA and DNA is in function. DNA has only one
function-STORING GENETIC INFORMATION in its sequence of nucleotide
bases. But there are three main kinds of ribonucleic acid, each of which has a specific
job to do.
Ribosomal RNAs-exist outside the nucleus in the cytoplasm of a cell in structures
called ribosomes. Ribosomes are small, granular structures where protein synthesis
takes place.Each ribosome is a complex consisting of about 60% ribosomal RNA
(rRNA) and 40% protein.
Messenger RNAs-are the nucleic acids that "record" information from DNA in the
cell nucleus and carry it to the ribosomes and are known as messenger RNAs
(mRNA).
Transfer RNAs-The function of transfer RNAs (tRNA) is to deliver amino acids
one by one to protein chains growing at ribosomes.
Part I
Template and DNA-directed RNA polymerase
1.Template
The process of converting the information contained in a DNA segment into proteins
begins with the synthesis of mRNA molecules containing anywhere from several
hundred to several thousand ribonucleotides, depending on the size of the protein to
be made. Each of the 100,000 or so proteins in the human body is synthesized from a
different mRNA that has been transcribed from a specific gene on DNA.
One question which you must ask yourself is:
"Why do we need mRNA if DNA holds all the genetic information, the instructions
for the proteins the cell is supposed to produce?"
The answer for eukaryotic cells (those cells with a nucleus) is the importance of
DNA. If DNA is damaged in any way, then the coding sequence is changed and a
mutation could result which could greatly affect the cell or even the whole
organism! You'll learn more about this when we discuss mutations in class. Because
of this, the DNA should be protected as much as possible.
If the DNA were to venture out into the cytoplasm where the ribosomes are in order
to give the instructions for which proteins were to be made, then it would be more
vulnerable to damage from: chemicals ,UV light , or other agents.
This presents a problem, however...
How is the DNA supposed to get the information it encodes out to the ribosomes
which carry out the instructions in the cytoplasm?
The answer is that there must be a MESSENGER. This messenger is mRNA!
So, how is mRNA made?
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Messenger RNA is synthesized in the cell nucleus by transcription of DNA, a process
similar to DNA replication. As in replication, a small section of the DNA double
helix unwinds, and the bases on the two strands are exposed. RNA nucleotides
(ribonucleotides) line up in the proper order by hydrogen-bonding to their
complementary bases on DNA, the nucleotides are joined together by a DNA
dependent RNA polymerase enzyme, and mRNA results.
UNLIKE what happens in DNA replication where both strands are copied, only ONE
of the two DNA strands is transcribed into mRNA (remember that RNA is a
single-stranded molecule). Asymmetric transcription：The two complementary DNA
strands have different roles in transcription. The strand that serves as template for
RNA synthesis is called the template strand(also known as the sense strand). The
DNA strand complementary to the template, the nontemplate strand, or coding strand
(also called the informational or antisense strand). Since the template strand and the
coding strand are complementary, and since the template strand and the mRNA
molecule are also complementary, it follows that the messenger RNA molecule
produced during transcription is a copy of the DNA coding strand! It is called this
because, with the exception of T for U changes, it corresponds exactly to the
sequence of the primary transcript, which encodes the protein product of the gene.
2.DNA-directed RNA polymerase
All RNA polymerases are dependent upon a DNA template in order to synthesize
RNA. Both RNA and DNA polymerases can add nucleotides to an existing strand,
extending its length. However, there is a major difference between the two classes of
enzymes: RNA polymerases can initiate a new strand but DNA polymerases cannot.
Classes of RNA Polymerases
In prokaryotic cells, all 3 RNA classes are synthesized by a single polymerase. E.
coli has a single DNA-directed RNA polymerase that synthesizes all types of RNA.
E. coli RNA polymerase is composed of five subunits: twoαsubunits, and one for
eachβ,β', and σ subunit.β(151 kD) andβ' (156 kD) are significantly larger than
α(37 kD). The two α subunits are essential for assembly of the enzyme and
activation by some regulatory proteins. β’,functions in DNA binding,β binds the
nucleoside triphosphate substrates and interacts with σ. The σ subunit is also known
as the σ factor. It binds transiently to the core and directs the enzyme to specific
initiation sites on the DNA (described below). Several different forms of σ subunits
have been identified, with molecular weights ranging from 28 kD to 70 kD. These
five subunits(α2ββ'σ) constitute the RNA polymerase holoenzyme. Nucleotide
synthesis is carried out by four subunits(α2ββ') which together are called the core
polymerase. In this case, the holoenzyme includes the core polymerase and the σ
factor.
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In eukaryotic cells there are 3 distinct classes of RNA polymerase, RNA polymerase
(pol) I, II and III. However, the eukaryotic RNA polymerase does not contain any
subunit similar to the E. coli σ factor. Therefore, in eukaryotes, transcriptional
initiation should be mediated by other proteins.
(The capacity of the various polymerases to synthesize different RNAs was shown
with the toxin-amanitin. At low concentrations of toxin-amanitin synthesis of
mRNAs are affected but not rRNAs nor tRNAs. At high concentrations, both
mRNAs and tRNAs are affected. These observations have allowed the identification
of which polymerase synthesizes which class of RNAs.)
Each polymerase is responsible for the synthesis of a different class of RNA.
RNA pol I is responsible for rRNA synthesis (excluding the 5S rRNA).There are 4
major rRNAs in eukaryotic cells designated by there sedimentation size. The 28S, 5S
5.8S RNAs are associated with the large ribosomal subunit and the 18S rRNA is
associated with the small ribosomal subunit.
RNA pol II synthesizes the mRNAs and some of the small nuclear RNAs (snRNAs)
involved in RNA splicing. It is undoubtedly the most important among the three
classes of RNA polymerases.
RNA pol III synthesizes the tRNAs, the 5S rRNA and some snRNAs.
But how do the polymerase know where to begin?
In other words, where does one gene start and stop and the next one begin? The
starting point of a gene is marked by a certain base sequence which is called a
promoter site. Analysis and comparison of sequences in many different bacterial
promoters have revealed similarities in two short sequences located about 10 and 35
base pairs away from the point where RNA synthesis is initiated.By convention the
base pair that begins an RNA molecule is given the number +1, so these sequences
are commonly called the -10 and -35 regions. The most common nucleotides form
what is called a consensus sequence.For most promoters in E. coli and related
bacteria, the consensus sequence for the -10 region also called the Pribnow box is
TATAAT, and the consensus sequence at the -35 region is TTGACA.
These sites are recognized by a factor called "σ". It is sigma's job to recognize the
promoter sites and "tell" the DNA dependent RNA polymerase where to begin
transcription. Once the RNA polymerase has been directed to the start point of the
gene by σ, the σ factor is released and the RNA polymerase carries out the process of
transcription.
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Part II Processes of Transcription
1.Prokaryotic Transcription
1.1 Initiation
Unlike DNA polymerase, RNA polymerase does not require a primer to initiate
synthesis. Initiation of RNA synthesis, however, occurs only at specific sequences
called promoters (described last). RNA synthesis usually starts with a GTP or ATP
residue, whose5'triphosphate group is not cleaved to release PP, form
5'pppGpN-OH3'; and remains intact throughout transcription. Since the role of σ
factor is mainly to initiate transcription, it will be released after first phosphodiester
bonds have been polymerized.
1.2 Elongation
This enzyme, DNA-directed RNA polymerase, requires, in addition to a DNA
template, all four ribonucleoside 5'-triphosphates (ATP, GTP, UTP, and CTP) as
precursors of the nucleotide units of RNA, as well as Mg2+. The purified enzyme also
contains Zn2+. The fundamental chemistry of RNA synthesis has much in common
with DNA synthesis. RNA polymerase elongates an RNA strand by adding
ribonucleotide units to the 3'-hydroxyl end of the RNA chain and thus builds RNA
chains in the 5'→3' direction. The 3'-hydroxyl group acts as nucleophile, attacking at
the a-phosphate of the incoming ribonucleoside triphosphate and releasing
pyrophosphate.
The overall reaction is
(NMP)n + NTP
(NMP)n+1 + PPi
RNA polymerase requires DNA for activity and is most active with a
double-stranded DNA as template.Only one of the two DNA strands is used as a
template, copied in the 3'→5' direction (antiparallel to the new RNA strand) just as
in DNA replication. Each nucleotide in the newly formed RNA is selected by
Watson-Crick base-pairing interactions; uridylate (U) residues are inserted in the
RNA opposite to adenylate residues in the DNA template, adenylate residues are
inserted opposite to thymidylate residues. Guanylate and cytidylate residues in
DNA specify cytidylate and guanylate, respectively, in the new RNA strand.
During transcription the new RNA strand base-pairs temporarily with the DNA
template to form a short length of hybrid RNA-DNA double helix, which is essential
to the correct readout of the DNA strand. The RNA in this hybrid duplex "peels off ''
shortly after its formation.
To enable RNA polymerase to synthesize an RNA strand complementary to one of
the DNA strands, the DNA duplex must unwind over a short distance, forming a
transcription "bubble."
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(Because the DNA is a helix, this process requires considerable rotation of the
nucleic acid molecules. Rotation is restricted in most DNAs by DNA-binding
proteins and other structural barriers, and a moving RNA polymerase generates
waves of positive supercoils ahead of and negative supercoils behind the point at
which transcription is occurring. This transcription-driven supercoiling of DNA has
been observed both in vitro and, in bacteria, in vivo. In the cell, the topological
problems caused by transcription are relieved through the action of
topoisomerases.)
Once begun, transcription in E. coli proceeds at a rate of about 50-100
nucleotides per second. Elongation of the RNA strand continues until the core
polymerase reaches the termination site.
1.3 Termination
Following termination the core polymerase dissociates from the template. The core
and sigma subunit can then reassociate forming the holoenzyme again ready to
initiate another round of transcription.
In E. coli transcriptional termination occurs by both factor-dependent and
factor-independent means. Two structural features of all E. coli factor-independently
terminating genes have been identified. One feature is the presence of new segments
that are capable of forming a stem-loop structure in the RNA and the second is a
downstream A rich sequence in the template. The formation of the stem-loop in the
RNA destabilizes the association between polymerase and the DNA template. This is
further destabilized by the weaker nature of the AU base pairs that are formed,
between the template and the RNA, following the stem-loop. This leads to
dissociation of polymerase and termination of transcription. Most genes in E. coli
terminate by this method.
The promoter sites act as a "start sign". Similarly, there are other base sequences
at the end of a gene that signal a to mRNA synthesis. Just as there is a sigma factor
to help signal the beginning of a gene, another factor called "rho " aids in
terminating the process of transcription. Factor-dependent termination requires the
recognition of termination sequences by the termination protein, rho. When the end
of the gene is near, the rho factor binds to the mRNA (that's right, the mRNA, NOT
the DNA) and interacts with the RNA polymerase. The interaction of rho with the
RNA polymerase causes the enzyme to "fall off" the DNA template strand, thus
stopping transcription!
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2. Eukaryotic Transcription
Eukaryotic transcription is more complex than prokaryotic transcription and, until
recently, it has seemed that every eukaryotic gene was unique requiring its own
transcription machinery.
However, it is now possible to simplify the story somewhat. The promoters for
different genes are different. Each contains a combination of sites to which specific
protein factors bind. All of these factors help RNA polymerase to bind in the correct
place and to initiate transcription. However, the repertoire of transcription factors and
transcription factor binding sites is not unlimited.
Transcription exhibits several features that are distinct from replication:
1. Transcription initiates, both in prokaryotes and eukaryotes, from many more sites
than replication.
2. There are many more molecules of RNA polymerase per cell than DNA
polymerase.
3. RNA polymerase proceeds at a rate much slower than DNA polymerase
(approximately 50-100 bases/sec for RNA versus near 1000 bases/sec for DNA).
4. Finally the fidelity of RNA polymerization is much lower than DNA. This is
allowable since the aberrant RNA molecules can simply be turned over and new
correct molecules made.
5. Transcription does not require a primer, replication need.
Part III Posttranscriptional Processing of RNAs
When transcription of bacterial rRNAs and tRNAs is completed they are
immediately ready for use in translation. No additional processing takes place.
Translation of bacterial mRNAs can begin even before transcription is completed due
to the lack of the nuclear-cytoplasmic separation that exists in eukaryotes. The ability
to initiate translation of prokaryotic RNAs while transcription is still in progress
affords a unique opportunity for regulating the transcription of certain genes. An
additional feature of bacterial mRNAs is that most are polycistronic. This means that
multiple polypeptides can be synthesized from a single primary transcript.
Polycistronic mRNAs are very rare in eukaryotic cells but have been identified. The
mitochondrial genomes in mammals and the slime mold, Dictyostelium discoideum,
encode polycistronic mRNAs that are processed into primarily mono-, di-, and
tricistronic transcripts. In addition, several viruses encode polycistronic RNAs.
In contrast to bacterial transcripts, eukaryotic RNAs (all 3 classes) undergo
significant post-transcriptional processing. All 3 classes of RNA are transcribed from
genes that contain introns.
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The sequences encoded by the intronic DNA must be removed from the primary
transcript prior to the RNAs being biologically active. The process of intron removal
is called RNA splicing. Additional processing occurs to mRNAs. The 5' end of all
eukaryotic mRNAs are capped with a unique 5'→5' linkage to a 7-methylguanosine
residue. The capped end of the mRNA is thus, protected from exonucleases and more
importantly is recognized by specific proteins of the translational machinery.
1. 5'-Cap of Eukaryotic mRNA
Structure of the 5'-Cap of Eukaryotic mRNAs
2. 3' poly A tail
Messenger RNAs also are polyadenylated at the 3' end. A specific sequence,
AAUAAA, is recognized by the endonuclease activity of by polyadenylate
polymerase which cleaves the primary transcript approximately 11 - 30 bases 3' of
the sequence element. A stretch of 20 - 250 A residues is then added to the 3' end by
the polyadenylate polymerase activity. The poly(A) tail also is bound by a specific
protein. It is likely that poly(A) tail and their associated proteins help protect the
mRNA from enzymatic destruction.
3. modification of tRNA and rRNA
In addition to intron removal in tRNAs, extra nucleotides at both the 5' and 3' ends
are cleaved, the sequence 5'-CCA-3' is added to the 3' end of all tRNAs and several
nucleotides undergo modification. There have been more than 60 different modified
bases identified in tRNAs.
Both prokaryotic and eukaryotic rRNAs are synthesized as long precursors termed
preribosomal RNAs. In eukaryotes a 45S preribosomal RNA serves as the precursor
for the 18S, 28S and 5.8S rRNAs.
The S number given each type of rRNA reflects the rate at which the molecules
sediment in the ultracentrifuge. The larger the number, the larger the molecule(but
not proportionally).
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4. Splicing of RNAs
A primary transcript for a eukaryotic mRNA typically contains sequences
encompassing one gene. The sequences encoding the polypeptide, however, usually
are not contiguous. Instead, in the majority of cases, the coding sequence is
interrupted by noncoding tracts called introns; the coding segments are called exons.
In a process called splicing, the introns are removed from the primary transcript and
the exons joined to form a contiguous sequence specifying a functional polypeptide.
The 2 most common are the group I and group II introns. Many of the group I and
group II introns are self-splicing, i.e. no additional protein factors are necessary for
the intron to be accurately and efficiently spliced out. The third class of introns is
also the largest class found in nuclear mRNAs. This class of introns undergoes a
splicing reaction similar to group II introns in that an internal lariat structure is
formed. However, the splicing is catalyzed by specialized RNA-protein complexes
called small nuclear ribonucleoprotein particles (snRNPs, pronounced snurps).
Part Ⅳ Reverse Transcription and ribozyme
After the RNA retrovirus enters a host cell, its genomic RNA will be transcribed
into a double stranded DNA and then integrated into the host DNA. The RNA to
DNA transcription is called reverse transcription. The entire process is catalyzed by
reverse transcriptase which has both DNA polymerase and RNase H activities.
RNA-directed DNA polymerases, also called reverse transcriptases. These
enzymes transcribe the viral RNA into DNA. This process can be used
experimentally to form complementary DNA. Many eukaryotic transposons are
related to retroviruses, and their mechanism of transposition includes an RNA
intermediate.
RNA-directed RNA polymerases, or replicases, are found in bacterial cells
infected with certain RNA viruses. They are template-specific for the viral RNA.
The existence of catalytic RNAs and pathways for the interconversion of RNA and
DNA has led to speculation that the earliest living things were made up entirely or
largely of RNA molecules that served both for information storage and for catalysis
of replication.
The self splicing introns and the RNA component of RNase P (the enzyme that
cleaves the 5' end of tRNA precursors) form a new class of biological catalysts called
ribozymes. These have the properties of true enzymes and are effective catalysts.
They promote two types of reaction, hydrolytic cleavage and transesterification,
using RNA as substrate.
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Summary
Transcription is very similar to replication in terms of chemical mechanism,
polarity (direction of synthesis), and use of a template. The two processes differ,
however, in that transcription does not require a primer, it generally involves only
short segments of a DNA molecule, and within those segments only one of the two
DNA strands serves as a template. Replication and transcription differ in one
important respect. During replication the entire chromosome is copied to yield
daughter DNAs identical to the parent DNA, whereas transcription is selective: only
particular genes or groups of genes are transcribed at any one time. The transcription
of DNA can therefore be regulated so that only genetic information needed by the
cell at a particular moment is transcribed. Specific regulatory sequences indicate the
beginning and end of the segments of DNA to be transcribed, as well as which DNA
strand is to be used as template.
Transcription is catalyzed by DNA-directed RNA polymerase, a complex enzyme
that synthesizes RNA complementary to a segment of one strand (the template
strand) of duplex DNA, starting from ribonucleoside 5'-triphosphates. To initiate
transcription, RNA polymerase binds to a DNA site called a promoter. Bacterial
RNA polymerase requires a special subunit for recognizing the promoter. As the first
committed step in transcription, binding of RNA polymerase to promoters is subject
to many forms of regulation.In E. coli transcriptional termination occurs by both
factor-dependent and factor-independent means. Eukaryotic cells have three different
types of RNA polymerases. Transcription stops at specific sequences called
terminators. Many copies of an RNA chain can be transcribed simultaneously from a
single gene.
Ribosomal RNAs and transfer RNAs are made from longer precursor RNAs that
are trimmed by nucleases, and some bases are modified enzymatically to yield the
mature RNAs. In eukaryotes, messenger RNAs are also formed from longer
precursors. Primary RNA transcripts often contain noncoding regions called introns,
which are removed by splicing. Messenger RNAs are also modified by addition of a
7-methylguanosine residue at the 5' end, and cleavage and polyadenylation at the 3'
end to form a long poly(A) tail.Many bases in tRNAs are also modified, mature
tRNAs are replete with unusual bases not found in other nucleic acids.
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Lesson plan for page
The processes of DNA and RNA synthesis are similar in some points.
(1) The general steps of initiation, elongation, and termination with 5’to 3’ polarity
(2) Large, multicomponent intiation cinokexes;
These processes differ in several important ways, including the following:
DNA
RNA
Precursors
dNTP
NTP
Polymerase
DNA Polymerase
RNA Polymerase
Base-pairing rules
Product
A-T, C-G
two-strands DNA
T-A, A-U, C-G
mRNA, tRNA, rRNA
two strand
asymmetric transcription
Template
(1) Ribonucleotides are used in RNA synthesis rather than deoxyribonucleotides;
(2)Adherence to Wastson-Crick base-pairing rules. But U replaces T as the
complementary base pair for A in RNA;
(3) Only a very small portion of the genome is transcribed into RNA, whereas the
entire genome must becopied during DNA replication;
(4) There is no proofreading function during RNA transcription.
(5) A primer is not involved in RNA synthesis.
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Select reading
Clinical Significances of Alternative and Aberrant Splicing
The presence of introns in eukaryotic genes would appear to be an extreme waste
of cellular energy when considering the number of nucleotides incorporated into the
primary transcript only to be removed later as well as the energy utilized in the
synthesis of the splicing machinery. However, the presence of introns can protect the
genetic makeup of an organism from genetic damage by outside influences such as
chemical or radiation. An additionally important function of introns is to allow
alternative splicing to occur, thereby, increasing the genetic diversity of the genome
without increasing the overall number of genes. By altering the pattern of exons,
from a single primary transcript, that are spliced together different proteins can arise
from the processed mRNA from a single gene. Alternative splicing can occur either
at specific developmental stages or in different cell types.
This process of alternative splicing has been identified to occur in the primary
transcripts from at least 40 different genes. Depending upon the site of transcription,
the calcitonin gene yields an RNA that synthesizes calcitonin (thyroid) or
calcitonin-gene related peptide (CGRP, brain). Even more complex is the alternative
splicing that occurs in the α-tropomyosin transcript. At least 8 different
alternatively spliced α-tropomyosin mRNAs have been identified.
Abnormalities in the splicing process can lead to various disease states. Many defects
in the β-globin genes are known to exist leading to b-thalassemias. Some of these
defects are caused by mutations in the sequences of the gene required for intron
recognition and, therefore, result in abnormal processing of the β-globin primary
transcript.
Patients suffering from a number of different connective tissue diseases exhibit
humoral auto-antibodies that recognize cellular RNA-protein complexes. Patients
suffering from systemic lupus erythematosis have auto-antibodies that recognize the
U1 RNA of the spliceosome.