Open Access
Nucleic Acids Research, volume 49, issue 1, pages 479-490
Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene
Publication type: Journal Article
Publication date: 2020-12-16
Journal:
Nucleic Acids Research
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 14.9
ISSN: 03051048, 13624962
PubMed ID:
33330934
Genetics
Abstract
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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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Kalinina M. A. et al. Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene // Nucleic Acids Research. 2020. Vol. 49. No. 1. pp. 479-490.
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Kalinina M. A., Skvortsov D., Kalmykova S., Ivanov T., Dontsova O., Pervouchine D. D. Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene // Nucleic Acids Research. 2020. Vol. 49. No. 1. pp. 479-490.
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TY - JOUR
DO - 10.1093/nar/gkaa1208
UR - https://doi.org/10.1093%2Fnar%2Fgkaa1208
TI - Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene
T2 - Nucleic Acids Research
AU - Kalinina, Marina A
AU - Dontsova, Olga
AU - Pervouchine, Dmitri D
AU - Skvortsov, Dmitry
AU - Kalmykova, Svetlana
AU - Ivanov, Timofei
PY - 2020
DA - 2020/12/16 00:00:00
PB - Oxford University Press
SP - 479-490
IS - 1
VL - 49
PMID - 33330934
SN - 0305-1048
SN - 1362-4962
ER -
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@article{2020_Kalinina,
author = {Marina A Kalinina and Olga Dontsova and Dmitri D Pervouchine and Dmitry Skvortsov and Svetlana Kalmykova and Timofei Ivanov},
title = {Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene},
journal = {Nucleic Acids Research},
year = {2020},
volume = {49},
publisher = {Oxford University Press},
month = {dec},
url = {https://doi.org/10.1093%2Fnar%2Fgkaa1208},
number = {1},
pages = {479--490},
doi = {10.1093/nar/gkaa1208}
}
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MLA
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Kalinina, Marina A., et al. “Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene.” Nucleic Acids Research, vol. 49, no. 1, Dec. 2020, pp. 479-490. https://doi.org/10.1093%2Fnar%2Fgkaa1208.