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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.
CONCLUSION: Our data suggest a novel function for amphibian lin28 proteins as positive regulators of mir-17∼92 family miRNAs. This article is protected by copyright. All rights reserved.
Bibliographical note(c) 2015 Wiley. This is an author produced version of a paper published in Developmental Dynamics. Uploaded in accordance with the publisher's self-archiving policy.
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