Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
Proc Natl Acad Sci U S A. 2022 Jan 25;119(4). doi: 10.1073/pnas.2121488119.
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.
细胞具有代偿机制，可协调主要生物过程的速率，从而在各种条件下实现生长。在这里，我们揭示了核内剪接/多聚腺苷酸化与细胞质中信使 RNA (mRNA) 周转之间的代偿联系。在全局范围内，半衰期差异两倍或更大的同基因 3' mRNA 异构体的稳态 mRNA 水平差异小于 2 的因子。此外，特定位置剪接/多聚腺苷酸化效率的提高与相应 3' mRNA 异构体的稳定性降低相关。这种剪接/多聚腺苷酸化与 mRNA 异构体半衰期之间的反比关系降低了 mRNA 异构体在稳态水平上的可变性，并且在所有测试的四种生长条件下都存在。这些观察结果表明，在核内剪接/多聚腺苷酸化过程中，mRNA 异构体以一种在易位到细胞质后仍能持续存在的方式被标记，并影响 mRNA 降解机制的活性，从而影响 mRNA 的稳定性。
