vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1029-8940-2025-70-2-146-160vestib-970Research ArticleСтатьиВлияние сохраняемых интронов на кодирующий потенциал молекул РНК в лейкозных клетках человекаEffect of retained introns on the coding potential of RNA molecules in human leukemia cellsГузоваЕ. В.HuzavaK. V.

Гузова Екатерина Витальевна – аспирант, мл. науч. сотрудник

пр. Независимости, 4, 220030, г. Минск

Katsiaryna V. Huzava – Postgraduate Student, Junior Researcher

4, Nezavisimosti Ave., 220030, Minsk

k.guzowwa0099@gmail.comГавричковА. А.GavrichkovA. A.

Гавричков Алексей Александрович – студент

пр. Независимости, 4, 220030, г. Минск

Aleksey A. Gavrichkov – Student

4, Nezavisimosti Ave., 220030, Minsk

gavrichkow@gmail.comИльюшёнокИ. Н.IlyushonakI. M.

Ильюшёнок Илья Николаевич – канд. биол. наук, доцент

пр. Независимости, 4, 220030, г. Минск

Ilya M. Ilyushonak – Ph. D. (Biol.), Associate Professor

4, Nezavisimosti Ave., 220030, Minsk

nov.ilyushonok@gmail.comРомановскаяТ. В.RamanouskayaT. A.

Романовская Татьяна Владимировна – канд. биол. наук, доцент

пр. Независимости, 4, 220030, г. Минск

Tatsiana V. Ramanouskaya – Ph. D. (Biol.), Associate Professor

4, Nezavisimosti Ave., 220030, Minsk

romanovskaya.t@mail.ruЛиховецМ. А.LikhavetsM. A.

Лиховец Максим Александрович – магистрант

пр. Независимости, 4, 220030, г. Минск

Maksim A. Likhavets – Master Student

4, Nezavisimosti Ave., 220030, Minsk

likhovetsmax@gmail.comСкакунВ. В.SkakunV. V.

Скакун Виктор Васильевич – канд. физ.-мат. наук, доцент

пр. Независимости, 4, 220030, г. Минск

Victor V. Skakun – Ph. D. (Math.), Associate Professor

4, Nezavisimosti Ave., 220030, Minsk

Skakun@bsu.byЯцковН. Н.YatskouM. M.

Яцков Николай Николаевич – канд. физ.-мат. наук, доцент, заведующий кафедрой

пр. Независимости, 4, 220030, г. Минск

Mikalai M. Yatskou – Ph. D. (Math.), Associate Professor, Head of the Department

4, Nezavisimosti Ave., 220030, Minsk

Yatskou@bsu.byГриневВ. В.GrinevV. V.

Гринев Василий Викторович – канд. биол. наук, доцент

пр. Независимости, 4, 220030, г. Минск

Vasily V. Grinev – Ph. D. (Biol.), Associate Professor

4, Nezavisimosti Ave., 220030, Minsk

grinev_vv@bsu.byБелорусский государственный университетBelarusian State University202508052025702146160Copyright © Гузова Е.В., Гавричков А.А., Ильюшёнок И.Н., Романовская Т.В., Лиховец М.А., Скакун В.В., Яцков Н.Н., Гринев В.В., 20252025Гузова Е.В., Гавричков А.А., Ильюшёнок И.Н., Романовская Т.В., Лиховец М.А., Скакун В.В., Яцков Н.Н., Гринев В.В.Huzava K.V., Gavrichkov A.A., Ilyushonak I.M., Ramanouskaya T.A., Likhavets M.A., Skakun V.V., Yatskou M.M., Grinev V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/970

Сохранение интронов – один из типов альтернативного сплайсинга, который подразумевает образование молекул зрелых РНК, содержащих в своей структуре хотя бы одну интронную последовательность. Если интронная последовательность попадает в кодирующую часть мРНК, то она может поменять структуру, свойства и порой функциональные возможности соответствующего белка. Более того, некоторые белки такого рода могут быть иммуногенными и рассматриваются как потенциальные мишени для терапии ряда заболеваний. Однако в целом влияние сохранения интронов на кодирующий потенциал РНК до сих пор изучено слабо.

В настоящей работе изложены результаты комбинированного транскриптомно-протеомного исследования 3540 последовательностей интронов, сохраняемых в зрелых молекулах РНК генов, активных в лейкозных клетках человека. Проведена классификация таких интронов в соответствии с наличием у них кодирующего потенциала и описано 7 возможных способов влияния сохранения интронов на последующую трансляцию соответствующих транскриптов. Выявлено 56 интронных последовательностей, способных транслироваться, причем 3 из них – с образованием ранее неизвестных полипептидов.

Intron retention is a mode of alternative splicing in which at least one intron is retained in mature RNA molecules. The inclusion of an intron sequence within the coding region of the mRNA can change the structure, properties and, in some cases, the functions of the corresponding protein. Furthermore, some of these altered proteins can be immunogenic and are considered as potential targets for the treatment of a number of diseases. In general, however, the effect of intron retention on the coding potential of RNA molecules remains poorly studied.

This paper presents the results of a combined transcriptomic-proteomic study of 3540 intron sequences retained in mature RNA molecules of genes that are active in human leukemia cells. The introns were classified according to their coding potential and seven possible ways in which intron retention can influence the subsequent translation of the corresponding transcripts were described. A total of 56 translation-capable intronic sequences were identified, and 3 of them produce previously unknown polypeptides.

альтернативный сплайсинг РНКсохранение интронатранскриптомкодирующий потенциалпротеомбиоинформатический анализalternative RNA splicingintron retentiontranscriptomecoding potentialproteomebioinformatics analysisАвторы признательны доктору Хосе Марин-Рубио из Института биологических наук при Ньюкаслском университете (г. Ньюкасл, Великобритания), а также профессору Олафу Хайденрайху из Центра детской онкологии имени Принцессы Максимы (г. Утрехт, Нидерланды) за помощь в получении оригинальных протеомных данных для клеток Kasumi-1. Эта работа стала частью проектов «Разработка комплексного подхода по идентификации новых, зависимых от дифференциального сплайсинга, иммуногенных пептидов лейкозных клеток», выполняемого при финансовой поддержке Белорусского республиканского фонда фундаментальных исследований (грант № M23-056, № гос. регистрации 20231102), и «Разработка моделей, алгоритмов и программных средств для идентификации и аннотации сайтов генетического полиморфизма по данным геномного секвенирования», выполняемого в рамках подпрограммы «Междисциплинарные исследования и новые зарождающиеся технологии» ГПНИ «Конвергенция–2025» на 2021–2025 гг. (проект № 3.04.3.1, № гос. регистрации 20211918).The authors thank Dr. Jose Luis Marin-Rubio (Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom) as well as Professor Olaf Heidenreich (Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands) for assistance in obtai ning the original proteomic data for Kasumi-1 cells. 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The authors declare that there are no conflicts of interest present.