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Nucleic Acids Research, том 49, издание 1, номера страниц: 479-490

Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene

Тип документаJournal Article
Дата публикации2020-12-16
ИздательOxford University Press
Название журналаNucleic Acids Research
Квартиль по SCImagoQ1
Квартиль по Web of ScienceQ1
Импакт-фактор 202119.16
ISSN03051048, 13624962
Genetics
Краткое описание

The mammalian Ate1 gene encodes an arginyl transferase enzyme with tumor suppressor function that depends on the inclusion of one of the two mutually exclusive exons (MXE), exons 7a and 7b. We report that the molecular mechanism underlying MXE splicing in Ate1 involves five conserved regulatory intronic elements R1–R5, of which R1 and R4 compete for base pairing with R3, while R2 and R5 form an ultra-long-range RNA structure spanning 30 Kb. In minigenes, single and double mutations that disrupt base pairings in R1R3 and R3R4 lead to the loss of MXE splicing, while compensatory triple mutations that restore RNA structure revert splicing to that of the wild type. In the endogenous Ate1 pre-mRNA, blocking the competing base pairings by LNA/DNA mixmers complementary to R3 leads to the loss of MXE splicing, while the disruption of R2R5 interaction changes the ratio of MXE. That is, Ate1 splicing is controlled by two independent, dynamically interacting, and functionally distinct RNA structure modules. Exon 7a becomes more included in response to RNA Pol II slowdown, however it fails to do so when the ultra-long-range R2R5 interaction is disrupted, indicating that exon 7a/7b ratio depends on co-transcriptional RNA folding. In sum, these results demonstrate that splicing is coordinated both in time and in space over very long distances, and that the interaction of these components is mediated by RNA structure.

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ГОСТ |
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1. Kalinina M. и др. Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene // Nucleic Acids Research. 2020. Т. 49. № 1. С. 479–490.
RIS |
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TY - JOUR

DO - 10.1093/nar/gkaa1208

UR - http://dx.doi.org/10.1093/nar/gkaa1208

TI - Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene

T2 - Nucleic Acids Research

AU - Kalinina, Marina

AU - Skvortsov, Dmitry

AU - Kalmykova, Svetlana

AU - Ivanov, Timofei

AU - Dontsova, Olga

AU - Pervouchine, Dmitri D

PY - 2020

DA - 2020/12/16

PB - Oxford University Press (OUP)

SP - 479-490

IS - 1

VL - 49

SN - 0305-1048

SN - 1362-4962

ER -

BibTex |
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@article{2020,

doi = {10.1093/nar/gkaa1208},

url = {https://doi.org/10.1093%2Fnar%2Fgkaa1208},

year = 2020,

month = {dec},

publisher = {Oxford University Press ({OUP})},

volume = {49},

number = {1},

pages = {479--490},

author = {Marina Kalinina and Dmitry Skvortsov and Svetlana Kalmykova and Timofei Ivanov and Olga Dontsova and Dmitri~D Pervouchine},

title = {Multiple competing {RNA} structures dynamically control alternative splicing in the human {ATE}1 gene}

}

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Kalinina, Marina et al. “Multiple Competing RNA Structures Dynamically Control Alternative Splicing in the Human ATE1 Gene.” Nucleic Acids Research 49.1 (2020): 479–490. Crossref. Web.