Сайты связывания miR-1322 в mRNA генов, участвующих в развитии нейродегенеративных и онкологических заболеваний
DOI:
https://doi.org/10.26577/EB-2017-4-1303Ключевые слова:
miR-1322, mRNA, ортологичные гены, социально значимые заболеванияАннотация
Установлено существование сайтов связывания miRNA не только в 3′-UTR, но и в 5′-UTR и CDS областях mRNA генов животных. Эффективность miRNA-индуцированной репрессии возрастает с увеличением числа сайтов связывания. Предполагается, что cвязывание miRNA может быть значительным, если ген содержит повторы последовательностей сайтов в кодирующей области. Было показано, что miR-1322 имеет полисайты в CDS областях mRNA десятков человеческих генов. Экспериментальная верификация функциональности большого числа сайтов является трудоемкой. Одним из способов определения достоверности сайтов для miRNA является доказательство существования данных сайтов в mRNA ортологичных генов и анализ их дивергенции в течение эволюции. Проведен анализ консервативности полисайтов miR-1322 в CDS mRNA ATN1, BCL6B, HTT, MAGI1, MLLT3, MN1, THAP11, TBP генов человека и их ортологов. Рассмотренные гены вовлечены в развитие нейродегенеративных и онкологических заболеваний. Результаты исследования показали, что полисайты для связывания miR-1322 обнаруживаются в mRNA ортологичных генов многих видов животных. В процессе эволюции число сайтов связывания изменяется, что, указывает на видовую зависимость эффективности регуляции экспрессии данных генов осуществляемой miR-1322. Помимо общего вклада в изучение механизмов патогенеза, вызванного участием ATN1, BCL6B, HTT, MAGI1, MLLT3, MN1, THAP11, TBP генов, проведенный нами анализ позволяет предложить адекватную экспериментальную модель животного для дальнейшего изучения регуляции экспрессии описанных генов посредством miR-1322.
Библиографические ссылки
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12 http://www.ncbi.nlm.nih.gov
13 http://mirbase.org
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30 Zhang G, Liu T, Wang Z. (2012) Downregulation of MAGI1 associates with poor prognosis of hepatocellular carcinoma. J Invest Surg, vol. 25, no. 2, pp. 93-99. DOI: 10.3109/08941939.2011.606875.
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21 Parker JB, Palchaudhuri S, Yin H, Wei J, Chakravarti D. A transcriptional regulatory role of the THAP11-HCF-1 complex in colon cancer cell function // Mol Cell Biol. – 2012. - Vol. 32, No 9. - P. 1654-70. DOI: 10.1128/MCB.06033-11.
22 Pina C, May G, Soneji S, Hong D, Enver T. MLLT3 regulates early human erythroid and megakaryocytic cell fate // Cell Stem Cell. – 2008. - Vol. 2, No. 3. - P. 264-73. DOI: 10.1016/j.stem.2008.01.013.
23 Schnall-Levin M, Zhao Y, Perrimon N, Berger B. Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3UTRs // Proc Natl Acad Sci USA. – 2010. - Vol. 107, No. 36. - P. 15751–6. DOI:10.1073/pnas.1006172107
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28 Wang W, Huang P, Wu P, et al. BCL6B expression in hepatocellular carcinoma and its efficacy in the inhibition of liver damage and fibrogenesis // Oncotarget. – 2015. – Vol. 6, No. 24. – P.20252-20265. DOI: 10.18632/oncotarget.3857
29 Zhang G, Wang Z. MAGI1 inhibits cancer cell migration and invasion of hepatocellular carcinoma via regulating PTEN // Zhong Nan Da Xue Xue Bao Yi Xue Ban. – 2011. - Vol. 36, No. 5. - P. 381-385 DOI:10.3969/j.issn.1672-7347.2011.05.002
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