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Extensive post-transcriptional regulation of miRNAs within
embryonic stem cells
Rupa Priti Sarkar, Geok Tan and Nick Dibb
Imperial College London, London, United Kingdom
MiRNAs are small non-coding RNAs that regulate diverse
biological functions including cell proliferation, apoptosis and
differentiation. Consequently it is not surprising that disruption
of miRNA synthesis plays an important role in various human
diseases including cancer. The biogenesis of miRNAs lends itself
to regulation at several stages, from transcription of the miRNA
gene to post-transcriptional control of primary, precursor and
mature miRNA transcripts.
We have analysed miRNAs that are uniquely expressed in either
human embryonic stem cells (ESCs) or differentiated neuronal
progenitors (NPCs). We have found that within ESCs miRNAs
can be regulated transcriptionally and post-transcriptionally
opposed to NPCs where miRNAs are regulated by transcription
only. MiRNAs with high expression in ESCs and NPCs were
investigated and out of these <40% of miRNA genes in ESCs are
transcribed but not processed to maturation; whereas in NPCs all
transcribed miRNAs genes are processed into mature miRNAs.
Flexible regulation of miRNAs in ESCs and strict transcriptional
regulation of miRNAs within NPCs may play a role in maintaining
pluripotency and aiding differentiation.
MiRNAs can be found in clusters sharing a single promoter,
despite this, individual miRNAs within clusters are often differentially expressed. We have evidence of extensive alternative
3’polyadenylation of primary miRNA transcripts that isolate
individual miRNA within clusters. Potentially alternative 3’polyadenylation may help regulate expression of a single miRNA within a
cluster, allowing fine tuning of miRNA expression.