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首页> 外文期刊>Molecular and Cellular Biology >CK2 Is Responsible for Phosphorylation of Human La Protein Serine-366 and Can Modulate rpL37 5′-Terminal Oligopyrimidine mRNA Metabolism
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CK2 Is Responsible for Phosphorylation of Human La Protein Serine-366 and Can Modulate rpL37 5′-Terminal Oligopyrimidine mRNA Metabolism

机译：CK2负责人类La蛋白丝氨酸366的磷酸化，并可以调节rpL37 5'-末端寡嘧啶mRNA的代谢

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La protein binds precursors to 5S rRNA, tRNAs, and other transcripts that contain 3′ UUU-OH and also promotes their maturation in the nucleus. Separate from this function, human La has been shown to positively modulate the translation of mRNAs that contain complex 5′ regulatory motifs that direct internal initiation of translation. Nonphosphorylated La (npLa) inhibits pre-tRNA processing, while phosphorylation of human La serine-366 (S366) promotes pre-tRNA processing. npLa was found specifically associated with a class of mRNAs that have unusually short 5′ untranslated regions comprised of terminal oligopyrimidine (5′TOP) tracts and that encode ribosomal proteins and translation elongation factors. Although La S366 represents a CK2 phosphorylation site, there was no evidence that CK2 phosphorylates it in vivo. We used the CK2-specific inhibitor, 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), and antisense-mediated knockdown to demonstrate that CK2 is responsible for La S366 phosphorylation in vivo. Hypophosphorylation was not associated with significant change in total La levels or proteolytic cleavage. Quantitative reverse transcription-PCR revealed increased association of the 5′TOP-mRNA encoding ribosomal protein L37 (rpL37) with La after TBB treatment. Transfection revealed more rpL37 mRNA associated with nonphosphorylatable La A366 than with La S366, concomitant with La A366-specific shift of a fraction of L37 mRNA off polysomes. The data indicate that CK2 phosphorylates La S366 in vivo, that this limits 5′TOP mRNA binding, and that increasing npLa leads to greater association with potentially negative effects on TOP mRNA translation. Consistent with data that indicate that phosphorylation reverses negative effects of npLa on tRNA production, the present data suggest that CK2 phosphorylation of La can affect production of the translational machinery.
机译：La蛋白将前体与5S rRNA，tRNA和其他包含3'UUU-OH的转录本结合，并促进它们在细胞核中的成熟。除此功能外，已显示人类La可以正向调节包含指导内部翻译的复杂5'调控基序的mRNA的翻译。非磷酸化的La（npLa）抑制了tRNA的加工，而人La丝氨酸366（S 366 ）的磷酸化促进了tRNA的加工。已发现npLa与一类mRNA特定相关，这些mRNA具有由末端寡聚嘧啶（5'TOP）末端组成的异常短的5'非翻译区，并编码核糖体蛋白和翻译延伸因子。尽管La S 366 代表CK2磷酸化位点，但没有证据表明CK2在体内将其磷酸化。我们使用了CK2特异性抑制剂4,5,6,7-四溴-2-氮杂苯并咪唑（TBB），以及反义介导的敲低实验来证明CK2负责体内La S 366 的磷酸化。次磷酸化与总La水平或蛋白水解裂解的显着变化无关。定量逆转录-PCR显示，TBB处理后，编码核糖体蛋白L37（rpL37）的5'TOP-mRNA与La的结合增加。转染显示与不可磷酸化La A 366 相关的rpL37 mRNA大于与La S 366 相关的蛋白，同时伴随La A 366 特异性移位L37 mRNA脱落的多核糖体。数据表明CK2在体内使La S 366 磷酸化，这限制了5'TOP mRNA的结合，而增加的npLa导致与对TOP mRNA翻译的潜在负面影响更大的关联。与表明磷酸化可逆转npLa对tRNA产生的负面影响的数据一致，本数据表明La的CK2磷酸化可影响翻译机制的产生。

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