Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post-transla...

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Main Authors: Helena Hernández, Olga V Makarova, Evgeny M Makarov, Nina Morgner, Yutaka Muto, Daniel Pomeranz Krummel, Carol V Robinson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-09-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007202&type=printable
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author Helena Hernández
Olga V Makarova
Evgeny M Makarov
Nina Morgner
Yutaka Muto
Daniel Pomeranz Krummel
Carol V Robinson
author_facet Helena Hernández
Olga V Makarova
Evgeny M Makarov
Nina Morgner
Yutaka Muto
Daniel Pomeranz Krummel
Carol V Robinson
author_sort Helena Hernández
collection DOAJ
description Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post-translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B'. Results also show that unstructured post-translationally modified C-terminal tails are responsible for the dynamics of Sm-B/B' and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.
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spelling doaj-art-7a58c3b07cf4409ba14d0db75c0593ea2025-08-20T02:32:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e720210.1371/journal.pone.0007202Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.Helena HernándezOlga V MakarovaEvgeny M MakarovNina MorgnerYutaka MutoDaniel Pomeranz KrummelCarol V RobinsonMost human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post-translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B'. Results also show that unstructured post-translationally modified C-terminal tails are responsible for the dynamics of Sm-B/B' and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007202&type=printable
spellingShingle Helena Hernández
Olga V Makarova
Evgeny M Makarov
Nina Morgner
Yutaka Muto
Daniel Pomeranz Krummel
Carol V Robinson
Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
PLoS ONE
title Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
title_full Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
title_fullStr Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
title_full_unstemmed Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
title_short Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
title_sort isoforms of u1 70k control subunit dynamics in the human spliceosomal u1 snrnp
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007202&type=printable
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