GSE21090
Functional non-canonical microRNAs in the mammalian hippocampus and cortex
Non-canonical microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) are distinct subclasses of small RNAs that bypass the DGCR8/Drosha Microprocessor but still require Dicer for their biogenesis.  What, if any, role they have in mammals remains unknown.  To identify potential roles for these Microprocessor-independent, Dicer-dependent small RNAs, we compared the phenotypes resulting from conditional deletion of dgcr8 versus dicer in post-mitotic neurons.  Loss of dicer resulted in an earlier lethality, more severe structural abnormalities, and increased apoptosis relative to dgcr8 loss.  Deep sequencing of small RNAs from the hippocampus and cortex of the conditional knockouts and control littermates identified multiple novel non-canonical microRNAs including new mirtrons H/ACA box snoRNA-derived small RNAs, and a previously unidentified mammalian subclass derived from C/D box snoRNAs.  These non-canonical miRNAs were expressed at high levels in the brain relative to other tissues. In contrast, we found no evidence for endo-siRNAs in the brain.  Taken together, our findings provide evidence for a diverse population of highly expressed non-canonical miRNAs that together play important functional roles in post-mitotic neurons. Overall design: Examination of small RNA populations in the hippocampus and cortex of 2 conditional knockout and control littermates