Impact of poly(A)-tail G-content on Arabidopsis PAB binding and their role in enhancing translational efficiency
Impact of poly(A)-tail G-content on Arabidopsis PAB binding and their role in enhancing translational efficiency
复制标题
Poly(A)-尾 G 含量对拟南芥 PAB 结合的影响及其在提高翻译效率中的作用
DOI：
10.1186/s13059-019-1799-8
复制
发表时间：
2019
期刊：
影响因子：
12.3
通讯作者：
Cao Xiaofeng
中科院分区：
文献类型：
--
作者：
Zhao Taolan;Huan Qing;Sun Jing;Liu Chunyan;Hou Xiuli;Yu Xiang;Silverman Ian M;Zhang Yi;Gregory Brian D;Liu Chun Ming;Qian Wenfeng;Cao Xiaofeng
聚腺苷化在真核生物产生成熟mrna中起关键作用。人们普遍认为，聚(A)结合蛋白（pab）与聚(A)尾mrna均匀结合，调节其稳定性和翻译效率。我们观察到广泛表达的拟南芥PABs （AtPAB2、AtPAB4和AtPAB8）的纯合三突变体具有胚胎致死性。为了了解分子基础，我们描述了这些pab的rna结合景观。atbab结合效率在基因之间的差异超过一个数量级。为了确定导致变异的序列，我们执行poly(A)-seq，直接对全长poly(A)尾部进行测序。超过10%的聚(A)尾部含有至少一种鸟苷(G)；其中g含量在0.8 ~ 28%之间。这些鸟苷经常将多聚(A)尾分裂成分散的A束，从而导致基因间atab结合效率的变化。核糖核酸测序和全基因组RNA稳定性分析表明，基因的atbab结合效率与翻译效率呈正相关，而与mRNA稳定性呈正相关。一致地，当AtPAB被耗尽时，具有较强AtPAB结合的基因表现出更大的翻译效率降低。本研究提供了一种通过g含量依赖的PAB结合调控基因翻译效率的新机制，为更好地理解poly(a) tail相关的基因表达调控铺平了道路。
Polyadenylation plays a key role in producing mature mRNAs in eukaryotes. It is widely believed that the poly(A)-binding proteins (PABs) uniformly bind to poly(A)-tailed mRNAs, regulating their stability and translational efficiency. We observe that the homozygous triple mutant of broadly expressed Arabidopsis thaliana PABs, AtPAB2, AtPAB4, and AtPAB8, is embryonic lethal. To understand the molecular basis, we characterize the RNA-binding landscape of these PABs. The AtPAB-binding efficiency varies over one order of magnitude among genes. To identify the sequences accounting for the variation, we perform poly(A)-seq that directly sequences the full-length poly(A) tails. More than 10% of poly(A) tails contain at least one guanosine (G); among them, the G-content varies from 0.8 to 28%. These guanosines frequently divide poly(A) tails into interspersed A-tracts and therefore cause the variation in the AtPAB-binding efficiency among genes. Ribo-seq and genome-wide RNA stability assays show that AtPAB-binding efficiency of a gene is positively correlated with translational efficiency rather than mRNA stability. Consistently, genes with stronger AtPAB binding exhibit a greater reduction in translational efficiency when AtPAB is depleted. Our study provides a new mechanism that translational efficiency of a gene can be regulated through the G-content-dependent PAB binding, paving the way for a better understanding of poly(A) tail-associated regulation of gene expression.