В. П. Сокольник
Республиканский научно-практический центр «Мать и дитя»
Первоначально Tudor-домен был открыт у дрозофилы как фактор, регулирующий эмбриональное развитие и фертильность. Позже белки, содержащие этот домен (TDRD), обнаружены у многих организмов, включая человека. Установлено, что TDRD-белки вовлечены во многие процессы, регулирующие метаболизм РНК. Они взаимодействуют с U-мя РНП (малые ядерные рибонуклеопротеины) и функционируют в сборке сплайсосом. Многие из белков, содержащих Tudor-домен, вовлечены в РНК-интерференцию и регулируют генную экспрессию на транскрипционном и посттранскрипционном уровнях. Недавние исследования показали, что большое количество TDRD функционируют в гонадах, где они регулируют гаметогенез и обеспечивают геномную стабильность. TDRD охарактеризованы также как белки, взаимодействующие с некоторыми факторами транскрипции и регулирующие модификацию хроматина. Обычно TDRD реализуют свои функции посредством присоединения к белкам, диметилированным по аргинину или лизину, и служат фактором доставки других белков в различные надмолекулярные комплексы, способствуя сборке и стабильности последних. TDRD могут также содержать дополнительные каталитические или функциональные домены и сами функционировать как белки-эффекторы. В данном обзоре мы приводим данные о биологической роли различных TDRD и их вовлечении в генез заболеваний человека.
ключевые слова: TDRD, РНК-метаболизм, хроматин, piРНК
Tudor domain containing proteins: biological functions and involvment in human diseases
V. P. Sokolnik
Tudor domain was first identified in the Drosophila as maternal factor that regulates embryonic development and fertility. Later Tudor domain containing proteins (TDRD) have been identified from essentially all eukaryotes, including human. Tudor domain proteins have been found to be involved in many processes that regulate the metabolism of RNA molecules. TDRD interact with U snRNP (small nuclear ribonucleoproteins) and function in spliceosome assembly and pre-mRNA splicing. Moreover, many Tudor domain proteins are involved in RNA interference and related pathways, in which small RNAs regulate gene expression, both post-transcriptionally and transcriptionally. TDRD regulate also chromatin activation or silencing and were characterized as transcription coactivators. Usually, Tudor domain proteins function as molecular adaptors, binding methylated arginine or lysine residues on their substrates to promote physical interactions and the assembly of macromolecular complexes. Many TDRD contain additional catalytic or functional domains and may function as effectors. In the present review, we will focus on the biological roles of different TDRD and their involvement in human diseases.
keywords: TDRD, RNA metabolism, chromatin, piRNA
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