functional hints for these novel candidates, Gemcitabine purchase we pre dicted the potential target genes of these miRNAs by using TargetScan, and carried out gene ontology en richment analysis with GOrilla of predicted target genes. We found that the potential function of Can didate 11 may be involved in regulating energy production and G protein coupled receptor signaling pathway. Con sidering that Candidate 11 has highest expression at P3, which is a peak stage for gliogenesis in cortex, we fur ther examined whether it affects the proliferation of glial cells using cultured rat C6 glial cell line. Interestingly, overexpression of Candidate 11 in C6 cells increased the cell proliferation, whereas suppressing the endogenous Candidate 11 by overexpressing a specific sponge RNA reduced the cell proliferation.

This result supports the notion that this novel miRNA may regulate the gliogenesis during cortical development. Potential stage specific RNA modification during cortical development Recent studies showed that miRNAs may undergo cleav age at the 3 end by specific exoribonuclease, resulting in the existence of multiple isoforms of variant lengths. We note that in all cortical RNA samples, variability in the length of miRNAs was detected as addition and or trimming of nucleotides at both 3 end and 5 end of mature miRNAs. Majority of known miR NAs underwent trimming at both 3 and 5 ends. However, trimming for several miRNAs including rno miR 1, rno miR 196a, rno miR 207, rno miR 347, and rno miR 742 was not detected, possibly due to the low abundance of trimmed isoforms rather than a selective protection of modifications.

Consistent with previous findings in Drosoph ila and in Human, we found that 3 end trimming is the most frequent type of isomiR in all cortical samples. This also suggests that there is no stage specific regulation of the trimming of miRNAs. Dataset Drug_discovery S4 provides a complete list of the name and relative abun dance of all detected isomiRs of known miRNAs. RNA editing has emerged as one important posttran scriptional mechanism that introduces nucleotide changes in RNA sequence, such as cytidine to uridine and adenosine to inosine via deamination, and may play important regulatory roles in the nervous system. Although the majority of editing events happens to pri miRNA and appear to affect the miRNA processing step, some nucleotide alterations happen in the seed sequence of mature miRNAs.

These edited mature miRNAs with altered seed sequence are likely to sup press a set of genes different from those targeted by un edited miRNAs. We sellekchem systemically examined the nucleotide changes of mature miRNAs by alignment of unannotated tags with mature sequence of miRNAs allowing one nucleotide mismatch. We discovered 160 miRNAs with single nucleotide modification located across the mature sequence with obviously higher frequency of modification detected at the seed and flanking regions. The existence of such a peak in nucleotide changes at seed and flanking sequence