let7

Let-7 is a family of microRNAs, small non-coding RNA molecules about 22 nucleotides in length, that regulate gene expression at the post-transcriptional level. It is among the best-studied microRNAs and is highly conserved across animals, with multiple let-7 family members encoded in many genomes.

Origin and evolution: Let-7 was first identified as a regulator of developmental timing in the nematode Caenorhabditis elegans and later found to be conserved across vertebrates. In humans and other mammals, the let-7 family comprises several related microRNAs (for example let-7a, let-7b, let-7c, etc.), produced from multiple genomic loci.

Biogenesis and mechanism: Like other microRNAs, let-7 genes are transcribed by RNA polymerase II, processed in the nucleus by Drosha, exported to the cytoplasm, and further processed by Dicer to generate mature let-7. The mature microRNA is incorporated into an Argonaute-containing RNA-induced silencing complex (RISC), where it binds to complementary sequences in the 3' untranslated regions of target mRNAs to repress translation or promote mRNA degradation.

Biological roles: In C. elegans, let-7 governs the timing of developmental events. In vertebrates, it participates in cell differentiation, development, and maintenance of tissue-specific gene expression. Let-7 also functions as a tumor suppressor in various contexts by regulating genes involved in cell proliferation and survival.

Targets and clinical relevance: Known targets include oncogenes such as members of the RAS family and HMGA2, among others. Reduced let-7 expression has been observed in multiple cancers and is associated with poor prognosis in some cases. Research continues into let-7 as a biomarker and as a potential component of therapeutic strategies, including the use of let-7 mimics.