lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development

TY - JOUR

T1 - lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development

AU - Warrander, Fiona

AU - Faas, Laura

AU - Kovalevskiy, Oleg

AU - Peters, Daniel

AU - Coles, Mark

AU - Antson, Alfred A

AU - Genever, Paul

AU - Isaacs, Harry V

N1 - (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.

PY - 2015/10/8

Y1 - 2015/10/8

N2 - 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.

AB - 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.

U2 - 10.1002/dvdy.24358

DO - 10.1002/dvdy.24358

M3 - Article

C2 - 26447465

SN - 1058-8388

JO - Developmental Dynamics

JF - Developmental Dynamics

ER -