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Title: The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Lastly, our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [1]
  1. Princeton Univ., Princeton, NJ (United States)
  2. National Institute of Health, Research Triangle Park, NC (United States)
Publication Date:
Grant/Contract Number:
W-31-109-Eng-38
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 19; Journal Issue: 1; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Princeton Univ., NJ (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; glorund; nanos; Drosophila; hnRNP; hnRNP F; hnRNP H; RNA-binding protein; translational control; translational repressor; post-transcriptional regulation; development
OSTI Identifier:
1399600
Alternate Identifier(s):
OSTI ID: 1367528

Tamayo, Joel V., Teramoto, Takamasa, Chatterjee, Seema, Hall, Traci M. Tanaka, and Gavis, Elizabeth R.. The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition. United States: N. p., Web. doi:10.1016/j.celrep.2017.03.022.
Tamayo, Joel V., Teramoto, Takamasa, Chatterjee, Seema, Hall, Traci M. Tanaka, & Gavis, Elizabeth R.. The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition. United States. doi:10.1016/j.celrep.2017.03.022.
Tamayo, Joel V., Teramoto, Takamasa, Chatterjee, Seema, Hall, Traci M. Tanaka, and Gavis, Elizabeth R.. 2017. "The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition". United States. doi:10.1016/j.celrep.2017.03.022.
@article{osti_1399600,
title = {The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition},
author = {Tamayo, Joel V. and Teramoto, Takamasa and Chatterjee, Seema and Hall, Traci M. Tanaka and Gavis, Elizabeth R.},
abstractNote = {The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Lastly, our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.},
doi = {10.1016/j.celrep.2017.03.022},
journal = {Cell Reports},
number = 1,
volume = 19,
place = {United States},
year = {2017},
month = {4}
}