The panorama of miRNA-mediated mechanisms in mammalian cells

Anna Stroynowska-Czerwinska,Agnieszka Fiszer,Wlodzimierz J. Krzyzosiak

doi:10.1007/s00018-013-1551-6

Abstract

MicroRNAs comprise a large family of short, non-coding RNAs that are present in most eukaryotic organisms and are typically involved in downregulating the expression of protein-coding genes. The detailed mechanisms of miRNA functioning in animals and plants have been under investigation for more than decade. In mammalian cells, miRNA guides the effector complex miRISC to bind with partially complementary sequences, usually within the 3′UTR of mRNAs, and inhibit protein synthesis with or without transcript degradation. In addition to these main mechanisms, several other modes of miRNA-mediated gene expression regulation have been described, but their scale and importance remain a matter of debate. In this review, we briefly summarize the pathway of miRNA precursor processing during miRNA biogenesis and continue with the description of the miRISC assembly process. Then, we present the miRNA-mediated mechanisms of gene expression regulation in detail, and we gather information concerning the proteins involved in these processes. In addition, we briefly refer to the current applications of miRNA mechanisms in therapeutic strategies. Finally, we highlight some of the remaining controversies surrounding the regulation of mammalian gene expression by miRNAs.

Highlights

MicroRNAs constitute a large family of short, non-coding RNAs (~22 nucleotides long) thatA
After gathering the relevant information on miRNA biogenesis and miRNA-induced silencing complex (miRISC) assembly, we focus on the recent understanding of cellular mechanisms of gene expression regulation by miRNAs
Numerous detailed questions remain unanswered, and among them are the following: Which factor is most important in determining the effect of miRNA activity? Is it the position of miRNA/mRNA mismatches? Is it the localization and number of miRNA-binding sites? How miRNAs within miRISCs find their binding sites on the transcript sequence is poorly understood

Summary

Introduction

Keywords miRNA · miRNA-mediated regulation of gene expression · Argonaute proteins · miRISC assembly · miRNA binding sites The bound miRNA strand (the “guide strand”) guides miRISC to interact with partially complementary sequences in target transcripts (mostly localized within the 3′UTR) and mainly triggers mRNA deadenylation and degradation or translation inhibition. MiRISC (guided by the single miRNA strand) finds partially complementary sequences in an mRNA and binds to the transcript (Fig. 2e).

Results

Conclusion