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Title: Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteins and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.
Authors:
 [1] ;  [2] ;  [2] ;  [2] ;  [3] ;  [3] ;  [4] ;  [5] ;  [4] ;  [6] ;  [2] ;  [7]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Biostatistics; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Dept. of Genome Dynamics
  2. Univ. of Connecticut Health Center, Farmington, Connecticut (United States). Dept. of Genetics and Genome Sciences and Inst. for Systems Genomics
  3. Harvard Medical School, Boston, MA (United States). Dept. of Cell Biology
  4. Harvard Medical School, Boston, MA (United States). Dept. of Cell Biology; Biogen Inc., Cambridge MA (United States)
  5. Univ. of California, Berkeley, CA (United States). Dept. of Biostatistics
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Dept. of Genome Dynamics; Univ. of California, Berkeley, CA (United States). Dept. of Statistics
  7. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Dept. of Genome Dynamics
Publication Date:
Grant/Contract Number:
AC02-05CH11231; U01 HG004271; U54 HG006944; K99 HG006698; 1U01HG007031-01; AC02-05CH11231/14-200
Type:
Accepted Manuscript
Journal Name:
Genome Research
Additional Journal Information:
Journal Volume: 25; Journal Issue: 11; Journal ID: ISSN 1088-9051
Publisher:
Cold Spring Harbor Laboratory Press
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Laboratory Directed Research and Development (LDRD) Program; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1256073
Alternate Identifier(s):
OSTI ID: 1474886

Stoiber, Marcus H., Olson, Sara, May, Gemma E., Duff, Michael O., Manent, Jan, Obar, Robert, Guruharsha, K. G., Bickel, Peter J., Artavanis-Tsakonas, Spyros, Brown, James B., Graveley, Brenton R., and Celniker, Susan E.. Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila. United States: N. p., Web. doi:10.1101/gr.182675.114.
Stoiber, Marcus H., Olson, Sara, May, Gemma E., Duff, Michael O., Manent, Jan, Obar, Robert, Guruharsha, K. G., Bickel, Peter J., Artavanis-Tsakonas, Spyros, Brown, James B., Graveley, Brenton R., & Celniker, Susan E.. Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila. United States. doi:10.1101/gr.182675.114.
Stoiber, Marcus H., Olson, Sara, May, Gemma E., Duff, Michael O., Manent, Jan, Obar, Robert, Guruharsha, K. G., Bickel, Peter J., Artavanis-Tsakonas, Spyros, Brown, James B., Graveley, Brenton R., and Celniker, Susan E.. 2015. "Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila". United States. doi:10.1101/gr.182675.114. https://www.osti.gov/servlets/purl/1256073.
@article{osti_1256073,
title = {Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila},
author = {Stoiber, Marcus H. and Olson, Sara and May, Gemma E. and Duff, Michael O. and Manent, Jan and Obar, Robert and Guruharsha, K. G. and Bickel, Peter J. and Artavanis-Tsakonas, Spyros and Brown, James B. and Graveley, Brenton R. and Celniker, Susan E.},
abstractNote = {In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteins and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.},
doi = {10.1101/gr.182675.114},
journal = {Genome Research},
number = 11,
volume = 25,
place = {United States},
year = {2015},
month = {8}
}