vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.195vavilov-851Research ArticleАнализ регуляторных последовательностейAnalysis of regulatory sequencesОценка трансляционной значимости характеристик нуклеотидной последовательности мРНК млекопитающих на основе данных рибосомного профилированияEstimation of translational importance of mammalian mRNA nucleotide sequence characteristics based on ribosome profiling dataВолковаО. А.VolkovaO. A.

Новосибирск, Россия

Novosibirsk, Russia

ov@bionet.nsc.ruКондрахинЮ. В.KondrakhinYu. V.

Новосибирск, Россия

Novosibirsk, Russia

ШариповР. Н.SharipovR. N.

Новосибирск, Россия

Novosibirsk, Russia

Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияInstitute of Cytology and Genetics SB RASRussian FederationФедеральное государственное бюджетное научное учреждение «Институт вычислительных технологий Сибирского отделения Российской академии наук» Общество с ограниченной ответственностью «Институт системной биологии»РоссияInstitute of Computational Technologies SB RAS Institute of Systems Biology, LtdRussian FederationФедеральное государственное бюджетное научное учреждение «Институт вычислительных технологий Сибирского отделения Российской академии наук» Общество с ограниченной ответственностью «Институт системной биологии» Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет»РоссияInstitute of Computational Technologies SB RAS Institute of Systems Biology, Ltd Novosibirsk State UniversityRussian Federation201602022017206779786Copyright © Волкова О.А., Кондрахин Ю.В., Шарипов Р.Н., 20172017Волкова О.А., Кондрахин Ю.В., Шарипов Р.Н.Volkova O.A., Kondrakhin Y.V., Sharipov R.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/851

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.

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 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.

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The authors declare that there are no conflicts of interest present.