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Target specificity among canonical nuclear poly(A) polymerases in plants modulates organ growth and pathogen response  

2013-08-27 09:13:06|  分类: 抗性基因 |  标签: |举报 |字号 订阅

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Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability, and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are coexpressed in different tissues. However, in neither case is it known whether the isoforms fulfill different functions or polyadenylate distinct subsets of pre-mRNAs. Here we show that the three canonical nuclear PAPS isoforms in Arabidopsis are functionally specialized owing to their evolutionarily divergent C-terminal domains. A strong loss-of-function mutation in PAPS1 causes a male gametophytic defect, whereas a weak allele leads to reduced leaf growth that results in part from a constitutive pathogen response. By contrast, plants lacking both PAPS2 and PAPS4 function are viable with wild-type leaf growth. Polyadenylation of SMALL AUXIN UP RNA (SAUR) mRNAs depends specifically on PAPS1 function. The resulting reduction in SAUR activity in paps1 mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. This suggests the existence of an additional layer of regulation in plant and possibly vertebrate gene expression, whereby the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A) tail length and hence expression of specific subsets of mRNAs.
背景:
在高等真核生物中,mRNAs的选择性腺苷酸化(alternative polyadenylation) 是一种重要的转录后基因调控机制。在蛋白质生物合成的过程中,这是产生准备作翻译的成熟mRNA的方式的一部份。mRNA 前体(pre-mRNA)在剪接之前,先在其3’-末端的某个位置切开,再进行多聚腺苷化(polyadenylation),形成多聚腺苷酸 (poly(A))尾巴。在此过程中, 分裂/多聚腺苷酸特异性因子(cleavage/polyadenylation specificity factor,CPSF)直接识别poly(A)位点上游的AAUAAA 序列,即poly(A)加尾信号(polyadenylation signal, PAS);刺激分裂因子(cleavage stimulatory factor, CstF)主要识别下游的富含GU 或U 的序列,即下游调控元件(downstream element, DUE)。在哺乳动物中, PAS是存在于poly(A)位点上游10~30 nt 处非常保守的AAUAAA 序列,而位于poly(A)位点下游20~40 nt处的是富含U 的DUE。 间隔一定距离存在的PAS和DUE 是CPSF 和CstF 结合并形成稳定的RNACPSF-CstF 复合物所必需的,所以对PAS 和DUE序列的研究对理解多聚腺苷化过程而言非常重要。多聚腺苷酸尾(或聚A尾)不仅能够保护mRNA,免受核酸外切酶攻击,并且在转录终结、从细胞核输出mRNA及翻译过程都有十分重要的作用。在3’UTR区存在多个潜在polyA位点时,选择性多聚腺苷酸化以组织或疾病特异性的方式影响着基因的表达。(BY:www.ablife.cc
  • Son Lang Vi,
  • Gerda Trost,
  • Peggy Lange,
  • Hj?rdis Czesnick,
  • Nishta Rao,
  • Diana Lieber,
  • Thomas Laux,
  • William M. Gray,
  • James L. Manley,
  • Detlef Groth,
  • Christian Kappel,
  • and Michael Lenhard
PNAS 2013 110 (34) 13994-13999; published ahead of print August 5, 2013, doi:10.1073/pnas.1303967110

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1303967110/-/DCSupplemental.

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