Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that are about 22 nucleotides in length. They regulate gene expression post-transcriptionally by guiding the effector protein Argonaute to its target mRNA in a sequence-dependent manner, causing the translational repression and destabilization of the target mRNAs. Both Drosha and Dicer, members of the RNase III family proteins, are essential components in the canonical miRNA biogenesis pathway. miRNA is transcribed into primary-miRNA (pri-miRNA) from genomic DNA. Drosha then cleaves the flanking regions of pri-miRNA into precursor-miRNA (pre-miRNA), while Dicer cleaves the loop region of the pre-miRNA to form a miRNA duplex. Although the role of Drosha and Dicer in miRNA maturation is well known, the modulation processes that are important for regulating the downstream gene network are not fully understood. In this review, we summarized and discussed current reports on miRNA biogenesis caused by Drosha and Dicer. We also discussed the modulation mechanisms regulated by double-stranded RNA binding proteins (dsRBPs) and the function and substrate specificity of dsRBPs, including the TAR RNA binding protein (TRBP) and the adenosine deaminase acting on RNA (ADAR).
Highlights
MicroRNAs are single-stranded RNAs of approximately 22 nucleotides in length and are classified as small non-coding RNAs
The miRNAs regulate gene expression post-transcriptionally by a mechanism known as RNA silencing, where miRNA is loaded onto Argonaute (AGO), a core component of the miRNA-induced silencing complex [1]
Using RNA immunoprecipitation sequencing (RIP-seq), we recently demonstrated that the secondary structures of pre-miRNAs may differ in trans-activation response (TAR) RNA binding protein (TRBP)-bound and non-bound pre-miRNAs [93] (Figure 4)
Summary
MicroRNAs (miRNAs) are single-stranded RNAs of approximately 22 nucleotides in length and are classified as small non-coding RNAs. III family protein, the loop region ofto thegenerate pre-miRNA to generate a in miRNA duplex collaboration with the trans-activation response (TAR). Pri-miRNA is cleaved by a microprocessor complex consisting of Drosha and DGCR8 to produce pre-miRNA, which is transported from the nucleus to the cytoplasm by EXP5 coupled with GTP-bound Ran (RanGTP). The knockout of Drosha and Dicer resulted in global miRNA deficiencies, which suggests that both proteins are required for miRNA biogenesis [29,30,31,32,33,34] While both of them are classified as RNase III family proteins, their recognition mechanisms for substrates and cofactors differ greatly [35,36]. We introduce the processing machinery of Drosha and Dicer and the regulated substrate selectivity of Dicer
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