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Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT

Zhdanov, D.D.; Vasina, D.A.; Orlova, E.V.; Orlova, V.S.; Pokrovskaya, M.V.; Aleksandrova, S.S.; Sokolov, N.N.

Biomeditsinskaia Khimiia 62(5): 544-554

2016

ISSN/ISBN: 2310-6972
PMID: 27797329
Accession: 057220027
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Kataliticheskaia sub"edinitsa telomerazy cheloveka hTERT podvergaetsia al'ternativnomu splaĭsingu, chto privodit k potere ee funktsiĭ i snizheniiu telomeraznoĭ aktivnosti. Izvestno, chto v al'ternativnom splaĭsinge mRNK hTERT prinimaet uchastie apoptoticheskaia éndonukleaza EndoG. Nami izuchena rol' EndoG v reguliatsii al'ternativnogo splaĭsinga mRNK hTERT. Pokazano, chto sverkhékspressiia EndoG v kletkakh kartsinomy kishechnika CaCo-2, a takzhe obrabotka kletochnykh iader i tsitoplazmy rekombinantnoĭ EndoG i inkubatsiia iader s RNK, rasshcheplennoĭ rekombinantnoĭ EndoG, privodit k povysheniiu urovnia varianta s b-deletsieĭ. V izolirovannykh kletochnykh iadrakh i transfitsirovannykh kletkakh al'ternativnyĭ splaĭsing mRNK hTERT indutsirovalsia 47-chlennym RNK-oligonukleotidom. Identifitsirovana dlinnaia nekodiruiushchaia RNK (1157 nukleotidov), iz kotoroĭ obrazuetsia aktivnyĭ 47-chlennyĭ RNK-oligonukleotid. Predlozhen sleduiushchiĭ mekhanizm splaĭsinga mRNK hTERT: c kodiruiushcheĭ tsepi gena hTERT sinteziruetsia pre-mRNK, a s matrichnoĭ – dlinnaia nekodiruiushchaia RNK; EndoG vyrezaet iz dlinnoĭ nekodiruiushcheĭ RNK 47-chlennyĭ oligonukleotid, komplementarnyĭ pre-mRNK hTERT, v meste soedineniia ékzona 8 i introna 8. Vzaimodeĭstvie étogo oligonukleotida s pre-mRNK hTERT indutsiruet al'ternativnyĭ splaĭsing.

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Related References

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