Control of developmental timing by small temporal RNAs: a paradigm for RNA‐mediated regulation of gene expression

Abstract

Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3' untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known for their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms.

The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis

“…stRNAs are noncoding RNAs that are synthesized as 60-70-nt precursors. These pre-stRNAs are processed into ∼21-nt RNAs that bind complementary sites in the 3Ј UTRs of target genes, inhibiting their expression at the level of protein synthesis (for review on stRNAs, see Banerjee and Slack 2002).…”

“…In contrast to double-stranded siRNAs, which are processed by Dicer from perfectly paired duplexes, at least some miRNAs are processed from imperfectly paired hairpin loops to form single-stranded 21-24-nt products (for review, see Banerjee and Slack 2002). Given the emerging genetic and biochemical studies of siRNA-and miRNA-containing complexes, one may now speculate on potential roles of Argonaute family proteins in specifying the fate of these two separate classes of RNAs processed by Dicer.…”

Computational prediction of microRNA genes in silkworm genome

“…The founding members of miRNAs are lin-4 and let-7 in C. elegans (Lee et al, 1993;Reinhart et al, 2000), which are also called small temporal RNAs because their inactivative mutation affects developmental timing (Banerjee and Slack, 2002). Lin-4 and let-7 exerted their functions by complementing to 3′ untranslated region (3′ UTR) of target mRNAs and inhibiting their translation processes (Lee et al, 1993;.…”

Les microARN

“…Ces dernières années, deux nouvelles classes de petits ARN non codants (ARNnc) de 21 à 25nucléotides ont été caractérisées chez les métazoaires et chez les plantes: les ARN interférents (ARNsi, small interfering RNA) double brin et les microARN simple brin. Ces deux types d'ARNnc pourraient interagir avec leurs ARNm cibles selon deux modes différents pour provoquer leur dégradation, ou l'inhibition de leur traduction [1,2]. La biogenèse et l'activité biologique de ces ARNnc nécessitent la participation d'une ou de plusieurs ribonucléase(s) de type III, des protéines de la famille Argonaute et, pour certains ARNsi, des enzymes capables de synthétiser de l'ARN à partir d'une matrice ARN.…”