Function and Regulation of Let-7 Family microRNAs

Abstract

MicroRNAs (miRNAs) are a group of small noncoding RNAs capable of regulating specific gene expression. Let-7 miRNA was first discovered in Caenorhabditis elegans and it is highly conserved in human tissues. The human let- 7 family of miRNA contains 12 members of miRNA. Today, these members have become the most studied miRNAs and they have attracted attention of researchers in various fields, such as development, stem cell biology, aging, and metabolism. Furthermore, there is a large body of evidence linking the loss of let-7 expression and the development of poorly differentiated, aggressive cancers. In addition to the canonical biogenesis pathway, let-7 has been found to be regulated by protein factors, such as RNA binding proteins previously identified as regulators of protein-coding mRNAs. Moreover, the direct interaction between miRNAs has recently been identified as a novel pathway to control let-7 expression. In this review, we discuss the multifaceted roles of let-7 and provide an overview of its regulation at multiple levels.

Evolution of Dermatofibrosarcoma Protuberans to DFSP-Derived Fibrosarcoma: An Event Marked by Epithelial–Mesenchymal Transition–like Process and 22q Loss

“…Let-7 genes encode tumor suppressor miRNAs that control the expression of a number of proteins involved in proliferation and apoptosis, EMT, adhesion, and migration (34,35). Among others, let-7 miRNAs have been implicated in the regulation of components of the epigenetic machinery, namely EZH2 (36).…”

Let-7 Suppresses B Cell Activation through Restricting the Availability of Necessary Nutrients

“…However, much remains to be learned about their physiological roles. The let-7 miRNA family, initially identified as a regulator of developmental timing in Caenorhabditis elegans, consists of 12 members expressed from eight genomic loci in mice (let-7a-1, let-7a-2, let-7b, let-7c-1, let-7c-2, let-7d, let-7e, let-7f-1, let-7f-2, let-7g, let-7i, and miR-98), all of which share the same ''seed sequence'' (Reinhart et al, 2000;Su et al, 2012). The let-7a-1/let-7d/let-7f-1 cluster (denoted as let-7adf cluster), with three members let-7a-1, let-7f-1, and let7d, is an important cluster of the let-7 family, accounting for about 25% of total let-7 precursors (Wang et al, 2011).…”

Small Non-Coding RNAs in Regulation of Course and Therapeutic Efficacy in Acute Myeloid Leukemia

“…The Ago3-piRNA complex then directs cleavage of antisense piRNA precursors, generating antisense piRNAs for Aub. The 5′-ends of amplified secondary piRNAs are determined by Aub and Ago3 Slicer [22][23][24][25].…”