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Download Glimpses of a few literatures on snRNA
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Glimpses of a little literature on small RNA Ali Ghanbari March 2006 Ghanbari The antiquity of RNA-based evolution Gerald F. Joyce Departments of Chemistry and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (e-mail: [email protected]) NATURE | VOL 418 | 11 JULY 2002 | March 2006 Ghanbari The dawn of darwinian evolution A cluttered path to RNA RNA-catalysed RNA replication Metabolic function in the RNA world Transition to the DNA–protein world March 2006 Ghanbari 1960‘s ncRNA RNA, that catalyse nucleotide synthesis RNA polymerization,aminoacylation of transfer RNA and peptide bond formation 1982 Ribozyme RNAse ribonuclerase The discovery of RNA interference petunias 1990 March 2006 (PTGS) Ghanbari Some titles concerning about the small RNA fRNA sRNA smRNA ncRNA siRNA snRNA (small nucleus) scRNA snoRNA( small nucleolar RNAs) RNAi stRNA snmRNA March 2006 Ghanbari Recent efforts of several laboratories have brought together two fascinating forms of gene regulation: silencing genes by degrading their mRNAs,and blocking translation of specific mRNAs during development.Both of these processes involve very small RNAs,about 22nt in length. March 2006 Ghanbari RNA interference Gregory J. Hannon Cold Spring Harbour Laboratory, 1 Bungtown Road, Cold Spring Harbour, New York 11724, USA (e-mail: [email protected]) NATURE | VOL 418 | 11 JULY 2002 RNA interference: It’s a small RNA world Eric G. Moss Current Biology 2001, 11:R772–R775 Short RNAs regulate gene expression in many species. Some are generated from any double-stranded RNA and degrade complementary RNAs; others are encoded by genes and repress specific mRNAs. Both, it turns out, are processed and handled by similar proteins. These pathways offer a glimpse into a world of small RNAs. March 2006 Ghanbari To identify more small regulatory RNAs of the lin4/let-7 class in C. elegans, we used informatics and cDNA cloning to select C. elegans genomic sequences that exhibited four characteristics of lin4 and let-7: (i) expression of a mature RNA of ;22 nt in of a mature RNA of ;22 nt incoding) sequences; (iii) high DNA se-quence similarity between orthologs in C. elegans and a related species, Caenorhabditis briggsae; and (iv) processing of the ;22-ntmature RNA from a stem-loop precursor transcript of ;65 nt (2, 3). An Extensive Class of Small RNAs in Caenorhabditis elegans Rosalind C. Lee and Victor Ghanbari Ambros* March 2006 The first of these was that let-7 RNA is phylogenetically conserved—in size and nucleotide sequence- in essentially all the bilaterally symmetric animals (Pasquinelli et al., 2000 Nature). A second discovery that supported the relative ubiq-uity of tiny RNAs like lin-4 (1993)and let7(2000) was the finding that small antisense RNAs of about 22 nt in length (called siRNAs) are central to RNA interference (RNAi) (see Sharp, 2001 Gene Dev. and references therein). March 2006 Ghanbari alternative splicing For example, exons can be extended or shortened, skipped or included, and introns can be removed or retained in the mRNA March 2006 Ghanbari A general mechanisms of alternative splicing RNA Silencing: The Genome’s Immune System Ronald H. A. Plasterk Scienc vol 296 2002 Genomes are databases sensitive to invasion by viruses. In recent years, a defense mechanism has been discovered, which turns out to be conserved among eukaryotes. The system can be compared to the immune system in several ways: It has speciÞcity against foreign elements and the ability to March 2006and raise a massive response Ghanbari against an invading nucleic amplify acid. The Over the years, a number of RNAs that do not function as messenger RNAs (mRNAs), transfer RNAs (tRNAs), or ribosomal RNAs (rRNAs) have been discovered,mostly fortuitously. The non-mRNAs have been given a variety of names (1, 2); the term small RNAs (sRNAs) has been pre-dominant in bacteria, whereas the term noncoding RNAs (ncRNAs) has been predominant in eukaryotes and will be used here. ncRNAs range in size from 21 to 25 nt for the large family of microRNAs (miRNAs) that modulate development in Caenorhabditis elegans, Drosophila, and mammals (3–8), up to ;100 to 200 nt for sRNAs commonly found as translational regulators in bacterial cells (9, 10) and to 10,000 nt for RNAs involved in gene silencing in higher eukaryotes (11–13). The functions described for ncRNAs thus far `are extremely varied (Table 1). March 2006 Ghanbari Table 1 Naturally occurring ribozymes and ribonucleoprotein enzymes Ribozyme Sequenced Size Activity (reaction product) examples (nt) Hammerhead 11 40 Self-cleavage via Hepatitis delta virus 2 90 transesterification (28,38 cyclic Hairpin 1 70 phosphate) Varkud satellite 1 160 Group I intron >1,500 210 Self-splicing via Group II intron >700 500 transesterification (38-OH) RNase P* >500 300 Pre-tRNA processing via hydrolysis (38-OH) Spliceosome* 70,50 180,100 RNA splicing via (U2+U6 snRNAs) transesterification (38-OH) Ribosome* >900 2,600 Peptidyl transfer (amide) March (23S2006 rRNA) Ghanbari Number of sequenced examples is a snapshot as of 2002 and is influenced by DNA-sequencing strategies and database upkeep; it may provide a rough indication of relative abundance. RNAs in any group vary in size; the size provided here indicates the lower end of the length distribution for the natural examples. Ribonucleoprotein enzymes. RNase P: bacterial and archaebacterial RNAs have the relevant activity in the absence of protein. Spliceosome: U2 and U6 small nuclear RNAs (snRNAs) alone show an activity related to the natural activity. Ribosome: no activity has yet been observed with protein-free, large-subunit rRNA. March 2006 Ghanbari The spreading signal may be the siRNAs itself, which could be continuously produced in cells that express dsRNA. It could also be envisioned that the siRNAs are replicated by the action of RdRPs. March 2006 Ghanbari Processes affected by ncRNAs. Process Example Function Transcription 184-nt E. coli 6S Modulates promoter use 331-nt human 7SK Inhibits transcription factor P-TEFb Steroid receptor elongation 875-nt human SRA coactivator Gene silencing chromosome I nactivation 16,500-nt human Xist Required for X- 100,000-nt human Air Required for autosomal gene imprinting Replication 451-nt human telomerase RNA Core of telomerase and telomere template RNA processing 377-nt E. coli RNase P Catalytic core of RNase 186-nt human U2 snRNA Core of spliceosome RNA modification of Directs 2’-O-ribose methylation target rRNA 189-nt S. cerevisiae snR8 H/ACA snoRNA Directs pseudouridylation of target rRNA 102-nt S. cerevisiae U18 C/D snoRNA 68-nt T. brucei gCYb gRNA excision of RNA stability 80-nt E. coli RyhB sRNA Eukaryotic miRNA? mRNA translation 109-nt E. coli OxyS occluding binding Directs the insertion and uridines Targets mRNAs for degradation? Targets mRNAs for degradation? Represses translation by ribosome 87-nt E. coli DsrA sRNA preventing inhibitory mRNA structure translation by pairing with end of target mRNA Protein stability on Protein Translocation recognition March 2006 membranes Activates translation by formation of an 22-nt C. elegans lin-4 miRNA Represses 39 363-nt E. coli tmRNA Directs addition of tag to peptides stalled ribosomes 114-nt E. coli 4.5S RNA Integral component of signal particle central to protein translocation across Ghanbari Table 1 Naturally occurring ribozymes and ribonucleoprotein enzymes Ribozyme Sequenced Size Activity (reaction product) March 2006 Ghanbari Higher eukaryotes can mount antiviral immune responses induced by dsRNA. This process, called RNA interference, is sequence specific and can therefore be used to target gene expression. Nature Immunology 3, 597 - 599 (2002) doi:10.1038/ni0702-597 March 2006 Ghanbari 1 According to one model for RNA silencing, there are two stages during which RNA is cleaved. a, In the first stage in Drosophila, the enzyme Dicer (identified by Bernstein et al.1) binds to double-stranded RNA produced by a virus or by mobile DNA, or introduced experimentally. Dicer cleaves the double-stranded RNA into fragments of 22 nucleotides each. b, Dicer then associates through its so-called PAZ domain with a relative of ARGONAUTE, another PAZ-domain-containing protein.c, This association would allow the 22nucleotide RNA to be transferred to an RNase associated with the ARGONAUTE relative, guiding the RNase to singlestranded messenger RNAs that match the 22-nucleotide RNA. The RNase would then cleave the single-stranded RNAs (not shown). Emerging clinical applications of RNA RNA as a protein antagonist Immunotherapy using mRNAtransfected dendritic cells March 2006 Ghanbari The small RNAs we know of may only be the tip of an iceberg. March 2006 Ghanbari Our intention: March 2006 Ghanbari March 2006 Ghanbari