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.