A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast.
A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast.
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DOI：
10.1073/pnas.2121488119
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发表时间：
2022-01-25
影响因子：
11.1
通讯作者：
Struhl K
中科院分区：
文献类型：
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作者：
Moqtaderi Z;Geisberg JV;Struhl K
细胞协调主要生物过程的速率，以响应环境条件，如营养物质的可用性和温度。在协调机制中，对一个过程的影响被对另一个过程的影响所补偿，从而维持适当的细胞平衡。在这里，我们揭示了在mRNA 3 '端产生聚(a)尾部的切割/聚腺苷化与mRNA衰变之间的代偿联系。这种代偿联系表明，在细胞核的裂解/聚腺苷化过程中，mRNA同工异构体在转运到细胞质时以一种持续存在的方式被标记。该标记影响mRNA降解机制的活性，从而影响mRNA的稳定性，并允许细胞在裂解/聚腺苷化速率随环境条件变化时保持相对相似的mRNA同工异构体水平。细胞具有补偿机制来协调主要生物过程的速率，从而允许在各种条件下生长。在这里，我们揭示了细胞核中的裂解/聚腺苷酸化与细胞质中的信使RNA （mRNA）转换之间的代偿联系。在全球范围内，具有两倍或更大半衰期差异的相同基因3 ' mRNA同种异构体的稳态mRNA水平差异显著小于2倍。此外，在特定位点的切割/聚腺苷化效率的提高与相应的3 ' mRNA异构体的稳定性降低有关。切割/聚腺苷化与mRNA异构体半衰期之间的这种反比关系降低了mRNA异构体稳态水平的可变性，并且在所有四种生长条件下都存在。这些观察结果表明，在细胞核的裂解/聚腺苷酸化过程中，mRNA同工异构体以一种方式被标记，这种方式在易位到细胞质时持续存在，并影响mRNA降解机制的活性，从而影响mRNA的稳定性。
Cells coordinate the rates of major biological processes in response to environmental conditions such as nutrient availability and temperature. Coordination mechanisms in which effects on one process are compensated for by effects on another process maintain an appropriate cellular balance. Here, we uncover a compensatory link between cleavage/polyadenylation, which generates poly(A) tails at mRNA 3′ ends, and mRNA decay. This compensatory link suggests that during cleavage/polyadenylation in the nucleus, mRNA isoforms are marked in a manner that persists upon translocation to the cytoplasm. This mark affects the activity of mRNA degradation machinery, thus influencing mRNA stability and allowing cells to maintain relatively similar levels of mRNA isoforms even when cleavage/polyadenylation rates change in response to environmental conditions. Cells have compensatory mechanisms to coordinate the rates of major biological processes, thereby permitting growth in a wide variety of conditions. Here, we uncover a compensatory link between cleavage/polyadenylation in the nucleus and messenger RNA (mRNA) turnover in the cytoplasm. On a global basis, same-gene 3′ mRNA isoforms with twofold or greater differences in half-lives have steady-state mRNA levels that differ by significantly less than a factor of 2. In addition, increased efficiency of cleavage/polyadenylation at a specific site is associated with reduced stability of the corresponding 3′ mRNA isoform. This inverse relationship between cleavage/polyadenylation and mRNA isoform half-life reduces the variability in the steady-state levels of mRNA isoforms, and it occurs in all four growth conditions tested. These observations suggest that during cleavage/polyadenylation in the nucleus, mRNA isoforms are marked in a manner that persists upon translocation to the cytoplasm and affects the activity of mRNA degradation machinery, thus influencing mRNA stability.
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影响因子：
7.7
作者：
Geisberg JV;Moqtaderi Z;Struhl K
通讯作者：
Struhl K
影响因子：
64.5
作者：
Geisberg JV;Moqtaderi Z;Fan X;Ozsolak F;Struhl K
通讯作者：
Struhl K
影响因子：
3.3
作者：
Parker, Roy
通讯作者：
Parker, Roy
影响因子：
5.3
作者：
Schwabish, Marc A.;Struhl, Kevin
通讯作者：
Struhl, Kevin
影响因子：
64.8
作者：
通讯作者：
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