Environmental influences on RNA processing: Biochemical, molecular and genetic regulators of cellular response.
Environmental influences on RNA processing: Biochemical, molecular and genetic regulators of cellular response.
复制标题
DOI：
10.1002/wrna.1503
复制
发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Luca F
中科院分区：
文献类型：
--
作者：
Pai AA;Luca F
RNA加工已成为调节细胞对环境扰动反应的关键机制步骤。最近的工作已经发现了转录组组成在环境扰动后的广泛重塑，并将这种分子可塑性的影响与健康和疾病结果联系起来。这些异构体变化及其潜在机制是多种多样的-涉及转录起始的替代位点，选择性剪接和mRNA 3′端的选择性切割。差异RNA加工的机制和后果已在一系列常见的环境损伤中得到表征，包括化学刺激、免疫刺激、热应激和癌症发病机制。在每种情况下，有扰动特定的贡献，本地（顺式）的监管元件或全球（反式）的因素和下游的后果。总的来说，很明显，同种型使用的选择涉及特定遗传元件（即，剪接位点，多聚腺苷酸化位点）和做出某些决定的时机（即，转录延伸率）。细胞对环境扰动的微调反应通常取决于细胞的遗传组成。个体间剪接变异的遗传分析已经确定了剪接的遗传效应，这些效应导致复杂性状的变异。最后，RNA加工分析的组织类型和环境条件的数量增加，需要开发适当的分析工具。大型数据集，新方法和探索条件的组合有望提供对RNA加工反应在人类表型变异中的作用的更深入理解。
RNA processing has emerged as a key mechanistic step in the regulation of the cellular response to environmental perturbation. Recent work has uncovered extensive remodeling of transcriptome composition upon environmental perturbation and linked the impacts of this molecular plasticity to health and disease outcomes. These isoform changes and their underlying mechanisms are varied - involving alternative sites of transcription initiation, alternative splicing, and alternative cleavage at the 3′ end of the mRNA. The mechanisms and consequences of differential RNA processing have been characterized across a range of common environmental insults, including chemical stimuli, immune stimuli, heat stress, and cancer pathogenesis. In each case, there are perturbation-specific contributions of local (cis) regulatory elements or global (trans) factors and downstream consequences. Overall, it is clear that choices in isoform usage involve a balance between the usage of specific genetic elements (ie. splice sites, polyadenlyation sites) and the timing at which certain decisions are made (ie. transcription elongation rate). Fine-tuned cellular responses to environmental perturbation are often dependent on the genetic makeup of the cell. Genetic analyses of inter-individual variation in splicing have identified genetic effects on splicing that contribute to variation in complex traits. Finally, the increase in the number of tissue types and environmental conditions analyzed for RNA processing is paralleled by the need to develop appropriate analytical tools. The combination of large datasets, novel methods and conditions explored promises to provide a much greater understanding of the role of RNA processing response in human phenotypic variation.
登录
查看更多内容
影响因子：
10.5
作者：
Boutz PL;Bhutkar A;Sharp PA
通讯作者：
Sharp PA
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
遗传和表观遗传变异对基因调节和剪接的组织特异性作用。
影响因子：
4.5
作者：
Gutierrez-Arcelus M;Ongen H;Lappalainen T;Montgomery SB;Buil A;Yurovsky A;Bryois J;Padioleau I;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Giger T;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
DOI：
10.1073/pnas.85.23.8998
发表时间：
1988-12-01
影响因子：
11.1
作者：
FROHMAN, MA;DUSH, MK;MARTIN, GR
通讯作者：
MARTIN, GR
DOI：
10.1073/pnas.1115761109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Barreiro, Luis B.;Tailleux, Ludovic;Gilad, Yoav
通讯作者：
Gilad, Yoav