In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 9 ( 2023-9-21), p. e3002302-
Abstract:
Organ laterality of vertebrates is specified by accelerated asymmetric decay of Dand5 mRNA mediated by Bicaudal-C1 (Bicc1) on the left side, but whether binding of this or any other mRNA to Bicc1 can be regulated is unknown. Here, we found that a CRISPR-engineered truncation in ankyrin and sterile alpha motif (SAM)-containing 3 (ANKS3) leads to symmetric mRNA decay mediated by the Bicc1-interacting Dand5 3′ UTR. AlphaFold structure predictions of protein complexes and their biochemical validation by in vitro reconstitution reveal a novel interaction of the C-terminal coiled coil domain of ANKS3 with Bicc1 that inhibits binding of target mRNAs, depending on the conformation of ANKS3 and its regulation by ANKS6. The dual regulation of RNA binding by mutually opposing structured protein domains in this multivalent protein network emerges as a novel mechanism linking associated laterality defects and possibly other ciliopathies to perturbed dynamics in Bicc1 ribonucleoparticle (RNP) formation.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002302
DOI:
10.1371/journal.pbio.3002302.g001
DOI:
10.1371/journal.pbio.3002302.g002
DOI:
10.1371/journal.pbio.3002302.g003
DOI:
10.1371/journal.pbio.3002302.g004
DOI:
10.1371/journal.pbio.3002302.g005
DOI:
10.1371/journal.pbio.3002302.g006
DOI:
10.1371/journal.pbio.3002302.g007
DOI:
10.1371/journal.pbio.3002302.s001
DOI:
10.1371/journal.pbio.3002302.s002
DOI:
10.1371/journal.pbio.3002302.s003
DOI:
10.1371/journal.pbio.3002302.s004
DOI:
10.1371/journal.pbio.3002302.s005
DOI:
10.1371/journal.pbio.3002302.s006
DOI:
10.1371/journal.pbio.3002302.s007
DOI:
10.1371/journal.pbio.3002302.s008
DOI:
10.1371/journal.pbio.3002302.s009
DOI:
10.1371/journal.pbio.3002302.s010
DOI:
10.1371/journal.pbio.3002302.r001
DOI:
10.1371/journal.pbio.3002302.r002
DOI:
10.1371/journal.pbio.3002302.r003
DOI:
10.1371/journal.pbio.3002302.r004
DOI:
10.1371/journal.pbio.3002302.r005
DOI:
10.1371/journal.pbio.3002302.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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