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SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing

RNA provides the framework for the assembly of some of the most intricate macromolecular complexes within the cell, including the spliceosome and the mature ribosome. The assembly of these complexes relies on the coordinated association of RNA with hundreds of trans-acting protein factors. While som...

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Autores principales: Floro, Jess, Dai, Anqi, Metzger, Abigail, Mora-Martin, Alexandra, Ganem, Neil J, Cifuentes, Daniel, Wu, Ching-Shyi, Dalal, Jasbir, Lyons, Shawn M, Labadorf, Adam, Flynn, Rachel L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450105/
https://www.ncbi.nlm.nih.gov/pubmed/34365507
http://dx.doi.org/10.1093/nar/gkab647
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author Floro, Jess
Dai, Anqi
Metzger, Abigail
Mora-Martin, Alexandra
Ganem, Neil J
Cifuentes, Daniel
Wu, Ching-Shyi
Dalal, Jasbir
Lyons, Shawn M
Labadorf, Adam
Flynn, Rachel L
author_facet Floro, Jess
Dai, Anqi
Metzger, Abigail
Mora-Martin, Alexandra
Ganem, Neil J
Cifuentes, Daniel
Wu, Ching-Shyi
Dalal, Jasbir
Lyons, Shawn M
Labadorf, Adam
Flynn, Rachel L
author_sort Floro, Jess
collection PubMed
description RNA provides the framework for the assembly of some of the most intricate macromolecular complexes within the cell, including the spliceosome and the mature ribosome. The assembly of these complexes relies on the coordinated association of RNA with hundreds of trans-acting protein factors. While some of these trans-acting factors are RNA-binding proteins (RBPs), others are adaptor proteins, and others still, function as both. Defects in the assembly of these complexes results in a number of human pathologies including neurodegeneration and cancer. Here, we demonstrate that Silencing Defective 2 (SDE2) is both an RNA binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability. Our data highlight SDE2 as a previously uncharacterized essential gene required for the assembly and maturation of the complexes that carry out two of the most fundamental processes in mammalian cells.
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spelling pubmed-84501052021-09-20 SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing Floro, Jess Dai, Anqi Metzger, Abigail Mora-Martin, Alexandra Ganem, Neil J Cifuentes, Daniel Wu, Ching-Shyi Dalal, Jasbir Lyons, Shawn M Labadorf, Adam Flynn, Rachel L Nucleic Acids Res RNA and RNA-protein complexes RNA provides the framework for the assembly of some of the most intricate macromolecular complexes within the cell, including the spliceosome and the mature ribosome. The assembly of these complexes relies on the coordinated association of RNA with hundreds of trans-acting protein factors. While some of these trans-acting factors are RNA-binding proteins (RBPs), others are adaptor proteins, and others still, function as both. Defects in the assembly of these complexes results in a number of human pathologies including neurodegeneration and cancer. Here, we demonstrate that Silencing Defective 2 (SDE2) is both an RNA binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability. Our data highlight SDE2 as a previously uncharacterized essential gene required for the assembly and maturation of the complexes that carry out two of the most fundamental processes in mammalian cells. Oxford University Press 2021-08-07 /pmc/articles/PMC8450105/ /pubmed/34365507 http://dx.doi.org/10.1093/nar/gkab647 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle RNA and RNA-protein complexes
Floro, Jess
Dai, Anqi
Metzger, Abigail
Mora-Martin, Alexandra
Ganem, Neil J
Cifuentes, Daniel
Wu, Ching-Shyi
Dalal, Jasbir
Lyons, Shawn M
Labadorf, Adam
Flynn, Rachel L
SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
title SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
title_full SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
title_fullStr SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
title_full_unstemmed SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
title_short SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
title_sort sde2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing
topic RNA and RNA-protein complexes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450105/
https://www.ncbi.nlm.nih.gov/pubmed/34365507
http://dx.doi.org/10.1093/nar/gkab647
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