Abstract

MicroRNAs (miRNAs) are small regulatory noncoding RNAs that are generated in the canonical RNA interference (RNAi) pathway. Drosha, DiGeorge syndrome critical region 8 (DGCR8) and Dicer are key players in miRNA biogenesis. Argonaute (Ago) proteins bind to miRNAs and are guided by them to find messenger RNA targets and carry out post-transcriptional silencing of protein-coding genes. Recently, emerging evidence suggests that RNAi factors have a range of noncanonical functions that are beyond miRNA biogenesis. These functions pertain to various biological processes, such as development, transcriptional regulation, RNA processing and maintenance of genome integrity. Here, we review recent literature reporting miRNA-independent, noncanonical functions of Drosha, DGCR8, Dicer and Ago proteins and discuss the importance of these functions.

Highlights

  • MicroRNAs are small regulatory noncoding RNAs that are generated in the canonical RNA interference (RNAi) pathway

  • RNAi is best demonstrated by miRNAs, a group of small noncoding RNAs (ncRNAs) of ~ 22 nucleotides in length, that guide effectors to messenger RNAs targets via complementary binding, leading to downregulation of target transcripts. miRNA-mediated gene regulation is regarded as a post-transcriptional gene silencing (PTGS) mechanism because it reduces protein levels by mRNA cleavage or translational inhibition [4]

  • We summarise the recent findings on the noncanonical functions of Drosha, DiGeorge syndrome critical region 8 (DGCR8), Dicer and Ago proteins in various biological processes

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Summary

Edited by Wilhelm Just

MicroRNAs (miRNAs) are small regulatory noncoding RNAs that are generated in the canonical RNA interference (RNAi) pathway. Argonaute (Ago) proteins bind to miRNAs and are guided by them to find messenger RNA targets and carry out post-transcriptional silencing of protein-coding genes. Emerging evidence suggests that RNAi factors have a range of noncanonical functions that are beyond miRNA biogenesis. These functions pertain to various biological processes, such as development, transcriptional regulation, RNA processing and maintenance of genome integrity. Certain noncoding RNAs (ncRNAs) are processed into small ncRNAs, which guide RNA-binding proteins to regulate gene expression in a process commonly known as RNA interference (RNAi). RNAi is best demonstrated by miRNAs, a group of small ncRNAs of ~ 22 nucleotides in length, that guide effectors to messenger RNAs (mRNAs) targets via complementary binding, leading to downregulation of target transcripts.

Noncanonical functions of RNAi proteins
UV irradiation
Various roles of Dicer
Increased usage of proximal APA site
Dicer in transcriptional regulation and RNA processing
Dicer in maintenance of genome integrity
Various roles of Ago proteins
Ago proteins in functions of tRNAderived fragments
Ago proteins in transcriptional regulation and RNA processing
DNA repair
Ago proteins in maintenance of genome integrity
Findings
Conclusions and perspectives
Full Text
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