脱腺苷酸酶与RNA代谢调控  

Regulation of RNA Metabolism by Deadenylases

作　　者：廖小燕 闫永彬[1] LIAO Xiao-Yan;YAN Yong-Bin(School of Life Sciences,Tsinghua University,Beijing 100084,China)

机构地区：[1]清华大学生命科学学院,北京100084

出　　处：《生物化学与生物物理进展》2023年第5期1002-1016,共15页Progress In Biochemistry and Biophysics

基　　金：国家重点研发计划(2020YFA0906900);国家自然科学基金(31870783,31370797,31170757,30770477)资助项目。

摘　　要：真核细胞中,RNA 3’端poly(A)或oligo(A)的特异性水解被称为脱腺苷酸化(deadenylation)。脱腺苷酸化的执行者被称为脱腺苷酸酶(deadenylase)。绝大多数真核细胞中都存在多种脱腺苷酸酶,其中CCR4-NOT复合体和PAN2-PAN3复合体负责细胞中大多数mRNA的非特异性降解,PARN和PNLDC1等参与了特定子集mRNA的降解和多种非编码RNA的生物合成。作为RNA水平的重要调控者之一,脱腺苷酸酶参与了几乎所有细胞生命活动和多种重要生理和病理过程。在真核细胞中,脱腺苷酸酶的分子调控机制可能是:细胞中的大量RNA结合蛋白是RNA命运调控的中心分子,一方面根据RNA的状态或细胞需求识别特定的靶标RNA子集,另一方面招募特定脱腺苷酸酶,对特定子集RNA的3’端进行降解或修剪,从而调控RNA的最终命运。细胞中十余种脱腺苷酸酶同工酶、上千种RNA结合蛋白以及多种多样的翻译后修饰构成了复杂的动态分子调控网络,帮助细胞在生长、增殖、分化、应激、死亡等重要生命活动中精确维持RNA稳态或快速转换基因表达谱。In eukaryotic cells,deadenylation is achieved by deadenylases,which are 3'-5'exonuclease that specifically degrade poly(A)or oligo(A)at the 3'-end of RNAs.Most eukaryotic cells contain more than a dozen of deadenylase isoenzymes.Among them,the CCR4-NOT complex and the PAN2-PAN3 complex are the main contributors of non-specific deadenylation of mRNAs,while PARN and PNLDC1 are involved in highly regulated deadenylation of mRNAs and the biogenesis of non-coding RNAs.Besides their roles in RNA metabolism,deadenylases are also regulators of transcription,translation efficiency,stress response,immunological response,genome integrity,and self-renewal and differentiation of stem cells.In vitro and in vivo studies have discovered that deadenylase activity can be modulated by low-molecular-weight compounds,intramolecular interactions between catalytic and non-catalytic/structural domains,post-translational modifications,and binding partners.By regulating the 3'-tail length of poly(A)or oligo(A)of RNAs,deadenylases have been found to participate in diverse cellular,physiological and pathological processes by modulating RNA homeostasis.Particularly,deadenylases are key players of development by regulating the clearance of maternal mRNAs,the expression of tissue-specific genes and the cross-talk with developmental signaling pathways.Recently,inherited mutations or aberrant expression of deadenylases has been associated with many diseases including telomere diseases,cardiovascular diseases,neurodevelopmental diseases,cancers,and metabolic diseases.The precise regulation of deadenylases in their diverse intracellular functions may be achieved by a complicated network composing of various cis-acting elements in the targeted RNAs,thousands of trans-acting RNA-binding proteins,and numerous post-translational modifications.In this network,RNA-binding proteins may act as hubs to bind with targeted RNAs with specific cis-acting elements and to recruit a distinct deadenylase via protein-protein interactions,and thereby to modulate RNA

关 键 词：脱腺苷酸酶 酶分子调控 MRNA降解 翻译效率 RNA代谢 RNA结合蛋白 

分 类 号：Q522[生物学—生物化学] Q55Q756