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lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development
Author(s) -
Warrander Fiona,
Faas Laura,
Kovalevskiy Oleg,
Peters Daniel,
Coles Mark,
Antson Alfred A.,
Genever Paul,
Isaacs Harry V.
Publication year - 2016
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24358
Subject(s) - lin28 , biology , microrna , xenopus , gene knockdown , embryonic stem cell , cold shock domain , microbiology and biotechnology , gene , genetics , rna , induced pluripotent stem cell
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. Developmental Dynamics 245:34–46, 2016 . © 2015 Wiley Periodicals, Inc.