регуляция экспрессии

МикроРНК: малые молекулы с большим значением

ОБЗОРЫ , ,

В.Н. Аушев

ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для цитирования: Аушев В.Н. МикроРНК: малые молекулы с большим значением. Клиническая онкогематология. 2015;8(1):1–12.

Для переписки: Василий Николаевич Аушев, канд. биол. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-17-64; e-mail: vaushev@gmail.com

РЕФЕРАТ

Обоснование. МикроРНК были впервые обнаружены как антисмысловые транскрипты у нематоды Caenorhabditis elegans, где они подавляли экспрессию генов, содержащих в мРНК комплементарные последовательности. Таким образом, данные молекулы наряду с короткими интерферирующими микроРНК являются основными медиаторами РНК-интерференции — универсального механизма регуляции экспрессии.

Результаты. МикроРНК представляют собой небольшие молекулы, транскрибируемые с геномной ДНК и подвергающиеся дальнейшему процессингу и экспорту в цитоплазму. Они могут входить в состав транскриптов, кодирующих белки, либо транскрибироваться с белок-некодирующих участков. Первичный процессинг может осуществляться с участием специализированного ферментного комплекса либо в ходе стандартного сплайсинга мРНК. После экспорта в цитоплазму промежуточный продукт подвергается окончательному процессингу с образованием активного РНК-белкового комплекса, способного связываться с комплементарными участками мРНК-«мишеней». Результатом такого связывания является подавление трансляции с данной мРНК. Сама мРНК во многих случаях может быть расщеплена за счет РНКазной активности комплекса.

Выводы. В геноме человека закодировано несколько тысяч микроРНК, образующих обширную регуляторную сеть, которая задействована в самых разных сигнальных путях и клеточных процессах. Нарушения микроРНК-регуляции вовлечены в развитие широкого спектра заболеваний, включая все типы неоплазий. МикроРНК имеют большое значение в онкологии, в частности в онкогематологии, как перспективные маркеры и потенциальные терапевтические агенты. К настоящему времени показано участие отдельных микроРНК в патогенезе большинства заболеваний системы крови. В ряде случаев предлагается использовать данные молекулы в качестве средств молекулярной диагностики и для определения прогноза заболевания.

Ключевые слова: микроРНК, регуляция экспрессии, онкомаркеры.

Получено: 16 июля 2014 г.

Принято в печать: 7 октября 2014 г.

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