U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.

U2 snRNP is an essential component of the spliceosome. It is responsible for branch point recognition in the spliceosome A-complex via base-pairing of U2 snRNA with an intron to form the branch helix. Small molecule inhibitors target the SF3B component of the U2 snRNP and interfere with A-complex fo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Veronica K Urabe, Meredith Stevers, Arun K Ghosh, Melissa S Jurica
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0976836617604d699a0dbbe03cebfff0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0976836617604d699a0dbbe03cebfff0
record_format	dspace
spelling	oai:doaj.org-article:0976836617604d699a0dbbe03cebfff02021-12-02T20:19:13ZU2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.1932-620310.1371/journal.pone.0258551https://doaj.org/article/0976836617604d699a0dbbe03cebfff02021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258551https://doaj.org/toc/1932-6203U2 snRNP is an essential component of the spliceosome. It is responsible for branch point recognition in the spliceosome A-complex via base-pairing of U2 snRNA with an intron to form the branch helix. Small molecule inhibitors target the SF3B component of the U2 snRNP and interfere with A-complex formation during spliceosome assembly. We previously found that the first SF3B inhibited-complex is less stable than A-complex and hypothesized that SF3B inhibitors interfere with U2 snRNA secondary structure changes required to form the branch helix. Using RNA chemical modifiers, we probed U2 snRNA structure in A-complex and SF3B inhibited splicing complexes. The reactivity pattern for U2 snRNA in the SF3B inhibited-complex is indistinguishable from that of A-complex, suggesting that they have the same secondary structure conformation, including the branch helix. This observation suggests SF3B inhibited-complex instability does not stem from an alternate RNA conformation and instead points to the inhibitors interfering with protein component interactions that normally stabilize U2 snRNP's association with an intron. In addition, we probed U2 snRNA in the free U2 snRNP in the presence of SF3B inhibitor and again saw no differences. However, increased protection of nucleotides upstream of Stem I in the absence of SF3A and SF3B proteins suggests a change of secondary structure at the very 5' end of U2 snRNA. Chemical probing of synthetic U2 snRNA in the absence of proteins results in similar protections and predicts a previously uncharacterized extension of Stem I. Because this stem must be disrupted for SF3A and SF3B proteins to stably join the snRNP, the structure has the potential to influence snRNP assembly and recycling after spliceosome disassembly.Veronica K UrabeMeredith SteversArun K GhoshMelissa S JuricaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258551 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Veronica K Urabe Meredith Stevers Arun K Ghosh Melissa S Jurica U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.
description	U2 snRNP is an essential component of the spliceosome. It is responsible for branch point recognition in the spliceosome A-complex via base-pairing of U2 snRNA with an intron to form the branch helix. Small molecule inhibitors target the SF3B component of the U2 snRNP and interfere with A-complex formation during spliceosome assembly. We previously found that the first SF3B inhibited-complex is less stable than A-complex and hypothesized that SF3B inhibitors interfere with U2 snRNA secondary structure changes required to form the branch helix. Using RNA chemical modifiers, we probed U2 snRNA structure in A-complex and SF3B inhibited splicing complexes. The reactivity pattern for U2 snRNA in the SF3B inhibited-complex is indistinguishable from that of A-complex, suggesting that they have the same secondary structure conformation, including the branch helix. This observation suggests SF3B inhibited-complex instability does not stem from an alternate RNA conformation and instead points to the inhibitors interfering with protein component interactions that normally stabilize U2 snRNP's association with an intron. In addition, we probed U2 snRNA in the free U2 snRNP in the presence of SF3B inhibitor and again saw no differences. However, increased protection of nucleotides upstream of Stem I in the absence of SF3A and SF3B proteins suggests a change of secondary structure at the very 5' end of U2 snRNA. Chemical probing of synthetic U2 snRNA in the absence of proteins results in similar protections and predicts a previously uncharacterized extension of Stem I. Because this stem must be disrupted for SF3A and SF3B proteins to stably join the snRNP, the structure has the potential to influence snRNP assembly and recycling after spliceosome disassembly.
format	article
author	Veronica K Urabe Meredith Stevers Arun K Ghosh Melissa S Jurica
author_facet	Veronica K Urabe Meredith Stevers Arun K Ghosh Melissa S Jurica
author_sort	Veronica K Urabe
title	U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.
title_short	U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.
title_full	U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.
title_fullStr	U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.
title_full_unstemmed	U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.
title_sort	u2 snrna structure is influenced by sf3a and sf3b proteins but not by sf3b inhibitors.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0976836617604d699a0dbbe03cebfff0
work_keys_str_mv	AT veronicakurabe u2snrnastructureisinfluencedbysf3aandsf3bproteinsbutnotbysf3binhibitors AT meredithstevers u2snrnastructureisinfluencedbysf3aandsf3bproteinsbutnotbysf3binhibitors AT arunkghosh u2snrnastructureisinfluencedbysf3aandsf3bproteinsbutnotbysf3binhibitors AT melissasjurica u2snrnastructureisinfluencedbysf3aandsf3bproteinsbutnotbysf3binhibitors
_version_	1718374208386367488

U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.

Ejemplares similares