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Инд. авторы: Волкова О.А., Кондрахин Ю.В., Шарипов Р.Н
Заглавие: Оценка трансляционной значимости характеристик нуклеотидной последовательности мрнк млекопитающих на основе данных рибосомного профилирования
Библ. ссылка: Волкова О.А., Кондрахин Ю.В., Шарипов Р.Н Оценка трансляционной значимости характеристик нуклеотидной последовательности мрнк млекопитающих на основе данных рибосомного профилирования // Вавиловский журнал генетики и селекции. - 2016. - Т.20. - № 6. - С.779-786. - ISSN 2500-0462. - EISSN 2500-3259.
Внешние системы: DOI: 10.18699/VJ16.195; РИНЦ: 27641079;
Реферат: rus: Известно, что характеристики 5'-нетранслируемой последовательности (5'-НТП) мРНК могут оказывать влияние на эффективность и специфичность инициации трансляции. Ранее знания о характеристиках 5'-НТП были получены теоретически и в экспериментах in vitro для мРНК отдельных генов, что не давало возможности оценить реальную трансляционную значимость ее параметров. Для выявления трансляционно-значимых характеристик 5'-НТП необходимо проанализировать их связь с трансляционной активностью соответствующих мРНК. Однако до недавнего времени доступные технологии не позволяли получить широкогеномные экспериментальные данные по эффективности трансляции. Благодаря появившейся технологии профилирования рибосом такие данные были получены для мРНК ряда эукариот. Использование их позволяет оценивать и выявлять трансляционно-значимые параметры мРНК, а также предсказывать эффективность трансляции мРНК на основании характеристик ее нуклеотидной последовательности. Цель нашей работы - определение трансляционной значимости отдельных характеристик нуклеотидной последовательности 5'-НТП мРНК на основании соответствующих экспериментальных данных по эффективности трансляции, рибосомному профилированию. Проведен статистический анализ отдельных характеристик нуклеотидных последовательностей мРНК человека и мыши; выявлена их взаимосвязь с соответствующими данными рибосомного профилирования. Были отобраны трансляционно-значимые параметры мРНК, тенденция влияния на эффективность трансляции которых наиболее значима и одинакова для всех трех проанализированных выборок: пурин в -3-позиции стартового кодона, вышележащие стартовые кодоны AUG в 5'-НТП, и комплементарные нуклеотиды G+C в составе 5'-НТП снижают эффективность трансляции; олигонуклеотид CCGCCA в районе 5'-НТП и олигонуклеотиды AAGAAA, AAGAAG, AAGCAG, AAAAAG в составе белок-кодирующей последовательности - усиливают. Разработаны с помощью платформы BioUML набор инструментов, позволяющий анализировать трансляционную значимость отдельных 5'-НТП мРНК, и программа для предсказания эффективности трансляции мРНК на основании ее нуклеотидной последовательности.
eng: It is known that the 5' untranslated region (5' UTR) mRNA characteristics can influence translation initiation efficiency and specificity. Previous knowledge about 5' UTR characteristics was obtained theoretically and in vitro for mRNA of individual genes. It did not allow systematic analysis of mRNA translationally important parameters. To identify the above mentioned 5' UTR characteristics, it is necessary to analyze their relationships with the translational activity of the corresponding mRNAs. Until recently, there were no experimental data on translation efficiency. Thanks to ribosome profiling technology, genome-wide experimental data of translation efficiency have been obtained for many eukaryotic mRNAs. Now it seems to be possible to reveal translationally important mRNA parameters and predict translation efficiency based on their nucleotide sequences. The aim of this study was to determine the translational significance of individual 5' UTR characteristics in accordance with experimental ribosome profiling data. A statistical analysis was carried out for revealing relationships between the human and mouse mRNA nucleotide sequence characteristics and ribosome profiling data. Some of the mRNA parameters influencing translation efficiency were most significant, and the same trends for all three samples analyzed were revealed: a purine at start codon context position -3, upstream AUG (Sl e-mail: ov@bionet.nsc.ru presence and G+C complementary nucleotide concentration reduce translation efficiency; whereas gexonucleotides CCGCCA (5' UTR) and AAGAAA, AAGAAG, AAGCAG, AAAAAG (CDS) increase translation efficiency. A toolkit that allows analyzing the importance of 5' UTR characteristics and a program for prediction of translation efficiency were developed on the base of the BioUML platform.
Ключевые слова: mRNA; 5 ''UTR; ribosome profiling; инициация трансляции; мРНК; 5''-НТП; Riboseq; профилирование рибосом; translation initiation;
Издано: 2016
Физ. характеристика: с.779-786
Цитирование:
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