A Regulator of Metabolic Reprogramming: MicroRNA Let-7

Abstract

Let-7, a gene firstly known to control the timing of Caenorhabditis elegans larval development does not code for a protein but instead produces small non-coding RNAs, microRNAs. Higher animals have multiple isoforms of mature let-7 microRNAs. Mature let-7 family members share the same "seed sequence" and distinct from each other slightly by 'non-seed' sequence region. Let-7 has emerged as a central regulator of systemic energy homeostasis and it displays remarkable plasticity in metabolic responses to nutrients availability and physiological activities. In this review, we discuss recent studies highlighting post-transcriptional mechanisms that govern metabolic reprogramming in distinct cells by let-7. We focus on the participation of the let-7 clusters in immune cells, and suggest that tissue-specific regulation of the let-7 clusters by engineered mouse models might impact metabolic homeostasis and will be required to elucidate their physiological and pathological roles in the in vivo disease models.

Figure 1

General features of mature let-7. (A) Chromosome location and distribution of let-7 genes in murine genome. (B) Mature sequence of murine let-7 genes. (C) Sequence comparison of mature let-7d across species.

Figure 2

Regulation of metabolic programs by let-7 in different tissues through targeting single or multiple genes.

Figure 3

Regulation of let-7 biogenesis by various factors.

Figure 4

Let-7 plays critical roles in different types of immune cells.