Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules
Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules
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DOI：
10.4161/rna.4.1.4364
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发表时间：
2007-01-01
期刊：
影响因子：
4.1
通讯作者：
Moss, Eric G.
中科院分区：
文献类型：
--
作者：
Balzer, Erica;Moss, Eric G.
Lin28是一种保守的细胞质蛋白，具有不寻常的RNA结合基序配对：冷休克结构域和一对逆转录病毒型CCHC锌指。线虫C.它是一种发育时间的调节器。在哺乳动物中，它富含各种类型的未分化细胞。然而，其分子功能尚不清楚。在多能哺乳动物细胞中，Lin28在RNA酶敏感复合物中与poly（A）结合蛋白以及蔗糖梯度的多聚体组分中观察到，表明其与翻译mRNA相关。在细胞应激时，Lin28定位于应激颗粒，其含有非翻译mRNA复合物。然而，Lin28也定位于细胞质加工体或P体，mRNA降解和microRNA调节的位点，与其调节mRNA翻译或稳定性的作用一致。突变分析表明，Lin28的保守的RNA结合结构域合作，把Lin28在mRNP，但只有CCHC结构域是需要本地化的P体。当两个RNA结合结构域都发生突变时，Lin28在细胞核中积累，表明它通常从细胞核穿梭到细胞质，与RNA结合。这些研究与Lin28结合细胞核中的mRNA并伴随它们到核糖体和P体的模型一致。我们认为Lin28影响分化过程中特定mRNA的翻译或稳定性。
Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA-binding motifs: a cold shock domain and a pair of retroviral-type CCHC zinc fingers. In the nematode C. elegans, it is a regulator of developmental timing. In mammals, it is abundant in diverse types of undifferentiated cells. However, its molecular function is unknown. In pluripotent mammalian cells, Lin28 is observed in RNase-sensitive complexes with poly(A)-binding protein, and in polysomal fractions of sucrose gradients, suggesting it is associated with translating mRNAs. Upon cellular stress, Lin28 locates to stress granules, which contain non-translating mRNA complexes. However, Lin28 also localizes to cytoplasmic processing bodies, or P-bodies, sites of mRNA degradation and microRNA regulation, consistent with it acting to regulate mRNA translation or stability. Mutational analysis shows that Lin28's conserved RNA binding domains cooperate to put Lin28 in mRNPs, but that only the CCHC domain is required for localization to P-bodies. When both RNA-binding domains are mutated, Lin28 accumulates in the nucleus, suggesting that it normally shuttles from nucleus to cytoplasm bound to RNA. These studies are consistent with a model in which Lin28 binds mRNAs in the nucleus and accompanies them to ribosomes and P-bodies. We propose that Lin28 influences the translation or stability of specific mRNAs during differentiation.