MicroRNAs, macrocontrol: Regulation of miRNA processing

Abstract

MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. Maturation of miRNAs comprises several regulated steps resulting in~22-nucleotide single-stranded mature miRNAs. Regulation of miRNA expression can occur both at the transcriptional level and at the post-transcriptional level during miRNA processing. Recent studies have elucidated specific aspects of the well-regulated nature of miRNA processing involving various regulatory proteins, editing of miRNA transcripts, and cellular location. In addition, single nucleotide polymorphisms in miRNA genes can also affect the processing efficiency of primary miRNA transcripts. In this review we present an overview of the currently known regulatory pathways of miRNA processing and provide a basis to understand how aberrant miRNA processing may arise and may be involved in pathophysiological conditions such as cancer.

Nuclear and cytoplasmic localization of neural stem cell microRNAs

“…Hence, given the substantial number of miRNAs, there presumably exists a staggering combinatorial network of miRNA-mediated post-transcriptional gene regulation (Selbach et al 2008). On top of the complexities of this network are questions about control of controllers, that is, control of biogenesis and processing of miRNAs, an area of much ongoing research (Slezak-Prochazka et al 2010).…”

Human mirtrons can express functional microRNAs simultaneously from both arms in a flanking exon-independent manner

“…[3][4][5][6] Most of these 20-24 nucleotide (nt) long molecules are formed via a canonical pathway, beginning with the transcription of a long primary precursor (pri-miRNA) with hairpin structure, followed by the cleavage of the nuclear RNase III-like enzyme Drosha, mediated by its partner protein, DGCR8. The so formed pre-miRNA is then recognized and transported by the Exportin-5 shuttle system to the cytoplasm where Dicer, another RNase III-type enzyme, produces the double-stranded miRNA:miRNA* duplex.…”

Downregulation of MicroRNA-152 contributes to high expression of DKK1 in multiple myeloma

“…As known, microRNAs are regulated at transcriptional level and at post-transcriptional level, 38 and mature miRNA has 2 arms, the 5p and 3p. 39 The primary hairpin miRNA transcript (pri-miRNA) is generated by RNA polymerase II or III from microRNA gene or introns in nucleus, cleaved and digested by the microprocessor complex (Drosha-DGCR8) to the pre-miRNA, which is exported to the cytoplasm, and finally the pre-miRNA is cleaved and digest by Dicer, TRBP and Paz proteins to produce a mature duplex miRNA. The 3p arm is generally considered nonfunctional as it does not incorporate into the RISC complex during biogenesis, few authors have considered 3p arm to be functional because of binding to the different Agonaute proteins.…”