How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing?
The splice sites (SSs) delimiting an intron are brought together in the earliest step of spliceosome assembly yet it remains obscure how SS pairing occurs, especially when introns are thousands of nucleotides long. Splicing occurs in vivo in mammals within minutes regardless of intron length, implyi...
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todo:paper_01689525_v32_n10_p596_Hollander2023-10-03T15:06:54Z How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? Hollander, D. Naftelberg, S. Lev-Maor, G. Kornblihtt, A.R. Ast, G. RNA polymerase II small nuclear ribonucleoprotein RNA polymerase II small nuclear ribonucleoprotein splicing factor U2AF U2AF2 protein, human carboxy terminal sequence chromatin chromatin structure exon genetic model genetic transcription human in vivo study intron kinetics length molecular evolution priority journal Review RNA binding RNA splicing RNA synthesis spliceosome exon genetics intron RNA splicing Chromatin Exons Humans Introns Ribonucleoprotein, U1 Small Nuclear Ribonucleoproteins, Small Nuclear RNA Polymerase II RNA Splicing Spliceosomes Splicing Factor U2AF The splice sites (SSs) delimiting an intron are brought together in the earliest step of spliceosome assembly yet it remains obscure how SS pairing occurs, especially when introns are thousands of nucleotides long. Splicing occurs in vivo in mammals within minutes regardless of intron length, implying that SS pairing can instantly follow transcription. Also, factors required for SS pairing, such as the U1 small nuclear ribonucleoprotein (snRNP) and U2AF65, associate with RNA polymerase II (RNAPII), while nucleosomes preferentially bind exonic sequences and associate with U2 snRNP. Based on recent publications, we assume that the 5′ SS-bound U1 snRNP can remain tethered to RNAPII until complete synthesis of the downstream intron and exon. An additional U1 snRNP then binds the downstream 5′ SS, whereas the RNAPII-associated U2AF65 binds the upstream 3′ SS to facilitate SS pairing along with exon definition. Next, the nucleosome-associated U2 snRNP binds the branch site to advance splicing complex assembly. This may explain how RNAPII and chromatin are involved in spliceosome assembly and how introns lengthened during evolution with a relatively minimal compromise in splicing. © 2016 Elsevier Ltd Fil:Kornblihtt, A.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01689525_v32_n10_p596_Hollander |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
RNA polymerase II small nuclear ribonucleoprotein RNA polymerase II small nuclear ribonucleoprotein splicing factor U2AF U2AF2 protein, human carboxy terminal sequence chromatin chromatin structure exon genetic model genetic transcription human in vivo study intron kinetics length molecular evolution priority journal Review RNA binding RNA splicing RNA synthesis spliceosome exon genetics intron RNA splicing Chromatin Exons Humans Introns Ribonucleoprotein, U1 Small Nuclear Ribonucleoproteins, Small Nuclear RNA Polymerase II RNA Splicing Spliceosomes Splicing Factor U2AF |
| spellingShingle |
RNA polymerase II small nuclear ribonucleoprotein RNA polymerase II small nuclear ribonucleoprotein splicing factor U2AF U2AF2 protein, human carboxy terminal sequence chromatin chromatin structure exon genetic model genetic transcription human in vivo study intron kinetics length molecular evolution priority journal Review RNA binding RNA splicing RNA synthesis spliceosome exon genetics intron RNA splicing Chromatin Exons Humans Introns Ribonucleoprotein, U1 Small Nuclear Ribonucleoproteins, Small Nuclear RNA Polymerase II RNA Splicing Spliceosomes Splicing Factor U2AF Hollander, D. Naftelberg, S. Lev-Maor, G. Kornblihtt, A.R. Ast, G. How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? |
| topic_facet |
RNA polymerase II small nuclear ribonucleoprotein RNA polymerase II small nuclear ribonucleoprotein splicing factor U2AF U2AF2 protein, human carboxy terminal sequence chromatin chromatin structure exon genetic model genetic transcription human in vivo study intron kinetics length molecular evolution priority journal Review RNA binding RNA splicing RNA synthesis spliceosome exon genetics intron RNA splicing Chromatin Exons Humans Introns Ribonucleoprotein, U1 Small Nuclear Ribonucleoproteins, Small Nuclear RNA Polymerase II RNA Splicing Spliceosomes Splicing Factor U2AF |
| description |
The splice sites (SSs) delimiting an intron are brought together in the earliest step of spliceosome assembly yet it remains obscure how SS pairing occurs, especially when introns are thousands of nucleotides long. Splicing occurs in vivo in mammals within minutes regardless of intron length, implying that SS pairing can instantly follow transcription. Also, factors required for SS pairing, such as the U1 small nuclear ribonucleoprotein (snRNP) and U2AF65, associate with RNA polymerase II (RNAPII), while nucleosomes preferentially bind exonic sequences and associate with U2 snRNP. Based on recent publications, we assume that the 5′ SS-bound U1 snRNP can remain tethered to RNAPII until complete synthesis of the downstream intron and exon. An additional U1 snRNP then binds the downstream 5′ SS, whereas the RNAPII-associated U2AF65 binds the upstream 3′ SS to facilitate SS pairing along with exon definition. Next, the nucleosome-associated U2 snRNP binds the branch site to advance splicing complex assembly. This may explain how RNAPII and chromatin are involved in spliceosome assembly and how introns lengthened during evolution with a relatively minimal compromise in splicing. © 2016 Elsevier Ltd |
| format |
JOUR |
| author |
Hollander, D. Naftelberg, S. Lev-Maor, G. Kornblihtt, A.R. Ast, G. |
| author_facet |
Hollander, D. Naftelberg, S. Lev-Maor, G. Kornblihtt, A.R. Ast, G. |
| author_sort |
Hollander, D. |
| title |
How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? |
| title_short |
How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? |
| title_full |
How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? |
| title_fullStr |
How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? |
| title_full_unstemmed |
How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing? |
| title_sort |
how are short exons flanked by long introns defined and committed to splicing? |
| url |
http://hdl.handle.net/20.500.12110/paper_01689525_v32_n10_p596_Hollander |
| work_keys_str_mv |
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1807320321145962496 |