Ontology highlight
ABSTRACT: Background
Lin28 proteins are post-transcriptional regulators of gene expression with multiple roles in development and the regulation of pluripotency in stem cells. Much attention has focussed on Lin28 proteins as negative regulators of let-7 miRNA biogenesis; a function that is conserved in several animal groups and in multiple processes. However, there is increasing evidence that Lin28 proteins have additional roles, distinct from regulation of let-7 abundance. We have previously demonstrated that lin28 proteins have functions associated with the regulation of early cell lineage specification in Xenopus embryos, independent of a lin28/let-7 regulatory axis. However, the nature of lin28 targets in Xenopus development remains obscure.Results
Here, we show that mir-17∼92 and mir-106∼363 cluster miRNAs are down-regulated in response to lin28 knockdown, and RNAs from these clusters are co-expressed with lin28 genes during germ layer specification. Mature miRNAs derived from pre-mir-363 are most sensitive to lin28 inhibition. We demonstrate that lin28a binds to the terminal loop of pre-mir-363 with an affinity similar to that of let-7, and that this high affinity interaction requires to conserved a GGAG motif.Conclusions
Our data suggest a novel function for amphibian lin28 proteins as positive regulators of mir-17∼92 family miRNAs.
SUBMITTER: Warrander F
PROVIDER: S-EPMC4982076 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
Warrander Fiona F Faas Laura L Kovalevskiy Oleg O Peters Daniel D Coles Mark M Antson Alfred A AA Genever Paul P Isaacs Harry V HV
Developmental dynamics : an official publication of the American Association of Anatomists 20151114 1
<h4>Background</h4>Lin28 proteins are post-transcriptional regulators of gene expression with multiple roles in development and the regulation of pluripotency in stem cells. Much attention has focussed on Lin28 proteins as negative regulators of let-7 miRNA biogenesis; a function that is conserved in several animal groups and in multiple processes. However, there is increasing evidence that Lin28 proteins have additional roles, distinct from regulation of let-7 abundance. We have previously demo ...[more]