vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-91vavilov-4405Research ArticleГЕНОМИКА И ТРАНСКРИПТОМИКАGENOMICS AND TRANSCRIPTOMICSКомпьютерный анализ показывает отличия митохондриальных микроРНК от остальных микроРНКComputer analysis shows differences between mitochondrial miRNAs and other miRNAsВорожейкинП. С.VorozheykinP. S.

Новосибирск

Novosibirsk

pavel.vorozheykin@gmail.comТитовИ. И.TitovI. I.

Новосибирск

Novosibirsk

Новосибирский национальный исследовательский государственный университетРоссияNovosibirsk State UniversityRussian FederationНовосибирский национальный исследовательский государственный университет; Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Курчатовский геномный центр ИЦиГ СО РАНРоссияNovosibirsk State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASRussian Federation202425012025288834842Copyright © Ворожейкин П.С., Титов И.И., 20252025Ворожейкин П.С., Титов И.И.Vorozheykin P.S., Titov I.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4405

Одним из подклассов микроРНК с до сих пор неизвестными специальными функциями являются митомиРы (mitomiRs) – митохондриальные микроРНК, которые в основном происходят из ядерной ДНК и импортируются в митохондрии, при этом изменение уровня их экспрессии ассоциировано с рядом заболеваний. Для выявления характерных особенностей митохондриальных микроРНК, отличающих их от остальных микроРНК, мы провели классификацию этих последовательностей с помощью метода случайного леса. Проведенный анализ впервые выявил достоверные различия между митомиРами и микроРНК по следующим характеристикам (по убыванию степени их важности в классификации): митомиРы имеют достоверно больший эволюционный возраст (низкий индекс филостратиграфического возраста, PAI), большее количество мишеней и ассоциаций с болезнями, в том числе митохондриальными (двусторонний точный тест Фишера, средние p-значения 1.82×10–89/1.13×10–96 для всех мРНК/болезней и 6.01×10–22/1.09×10–9 для митохондриальных); принадлежат к классу «циркулирующих» (среднее p-значение 1.20×10–56). Обнаруженные различия между митомиРами и остальными микроРНК могут помочь раскрыть способ доставки микроРНК в митохондрии, свидетельствуют об эволюционной консервативности и важности митомиРов в регулировании функций и метаболизма митохондрий, а в целом говорят о том, что митомиРы не являются случайными микроРНК. Информация о 1312 экспериментально подтвержденных последовательностях митомиРов для трех организмов (Homo sapiens, Mus musculus и Rattus norvegicus) собрана в базе mitomiRdb (https://mitomiRdb.org).

A subclass of miRNAs with as yet unknown specific functions is mitomiRs – mitochondrial miRNAs that are mainly derived from nuclear DNA and are imported into mitochondria; moreover, changes in the expression levels of mitomiRs are associated with some diseases. To identify the most pronounced characteristics of mitochondrial miRNAs that distinguish them from other miRNAs, we classified mitomiR sequences using the Random Forest algorithm. The analysis revealed, for the first time, a significant difference between mitomiRs and other microRNAs by the following criteria (in descending order of importance in the classification): mitomiRs are evolutionarily older (have a lower phylostratigraphic age index, PAI); have more targets and disease associations, including mitochondrial ones (twosided Fisher’s exact test, average p-values 1.82×10–89/1.13×10–96 for all mRNA/diseases and 6.01×10–22/1.09×10–9 for mitochondria, respectively); and are in the class of “circulating” miRNAs (average pvalue 1.20×10–56). The identified differences between mitomiRs and other miRNAs may help uncover the mode of miRNA delivery into mitochondria, indicate the evolutionary conservation and importance of mitomiRs in the regulation of mitochondrial function and metabolism, and generally show that mitomiRs are not randomly encountered miRNAs. Information on 1,312 experimentally validated mitomiR sequences for three organisms (Homo sapiens, Mus musculus and Rattus norvegicus) is collected in the mitomiRdb database (https://mitomiRdb.org).

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