Structural analyses of an RNA stability element interacting with poly(A).
Structural analyses of an RNA stability element interacting with poly(A).
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与 Poly(A) 相互作用的 RNA 稳定性元件的结构分析。
DOI：
10.1073/pnas.2026656118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Steitz,JoanA
中科院分区：
文献类型：
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作者：
Torabi,Seyed-Fakhreddin;Chen,Yen-Lin;Zhang,Kaiming;Wang,Jimin;DeGregorio,SuzanneJ;Vaidya,AnandT;Su,Zhaoming;Pabit,SuzetteA;Chiu,Wah;Pollack,Lois;Steitz,JoanA
顺式作用RNA元件对聚腺苷化RNA的稳定性调控至关重要。核表达元件（ENE）包含一个富含铀的内部环，两侧是短螺旋。ENE通过形成三联体结构隔离聚(A)尾部来稳定RNA，从而抑制快速去烯化依赖的衰变途径。基于结构的生物信息学研究在进化多样化的基因组中发现了许多类似ENE的元件，包括包含两个由短双螺旋区域分隔的ENE基序的亚类（双ENE [dENEs]）。本文研究了水稻转座因子（TWIFB1）在poly(a)结合前后（分别为~ 24 kDa和~ 33 kDa）的dENE结构。我们结合生化结构探测、小角度x射线散射（SAXS）和低温电子显微镜（cryo- em）研究了聚(A)结合后dENE的结构及其局部和全局结构变化。我们的数据揭示了1)poly(A)与dENE结合的方向性，以及2)dENE-poly(A)相互作用涉及一个基序，该基序保护poly(A)的3 * 7个腺苷酸。此外，我们证明了在poly(a)结合时，dENE不会经历剧烈的全局构象变化。这些发现与最近解决的dENE+聚(a)配合物的晶体结构一致。[j].科学通报，2011,(5):357 - 357。多聚(A) -RNA相互作用的其他模式的鉴定为更好地理解多聚(A)尾部生物学开辟了新的场所。
Cis-acting RNA elements are crucial for the regulation of polyadenylated RNA stability. The element for nuclear expression (ENE) contains a U-rich internal loop flanked by short helices. An ENE stabilizes RNA by sequestering the poly(A) tail via formation of a triplex structure that inhibits a rapid deadenylation-dependent decay pathway. Structure-based bioinformatic studies identified numerous ENE-like elements in evolutionarily diverse genomes, including a subclass containing two ENE motifs separated by a short double-helical region (double ENEs [dENEs]). Here, the structure of a dENE derived from a rice transposable element (TWIFB1) before and after poly(A) binding (∼24 kDa and ∼33 kDa, respectively) is investigated. We combine biochemical structure probing, small angle X-ray scattering (SAXS), and cryo‐electron microscopy (cryo-EM) to investigate the dENE structure and its local and global structural changes upon poly(A) binding. Our data reveal 1) the directionality of poly(A) binding to the dENE, and 2) that the dENE-poly(A) interaction involves a motif that protects the 3ʹ-most seven adenylates of the poly(A). Furthermore, we demonstrate that the dENE does not undergo a dramatic global conformational change upon poly(A) binding. These findings are consistent with the recently solved crystal structure of a dENE+poly(A) complex [S.-F. Torabiet al.,Science371, eabe6523 (2021)]. Identification of additional modes of poly(A)–RNA interaction opens new venues for better understanding of poly(A) tail biology.