Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, 430 E. 29th Street, New York, NY 10016, USA.
Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, 430 E. 29th Street, New York, NY 10016, USA.
Mol Cell. 2019 Apr 18;74(2):284-295.e5. doi: 10.1016/j.molcel.2019.01.044. Epub 2019 Mar 6.
The diversity of mRNA lifetimes in bacterial cells is difficult to reconcile with the relaxed cleavage site specificity of RNase E, the endonuclease most important for governing mRNA degradation. This enzyme has generally been thought to locate cleavage sites by searching freely in three dimensions. However, our results now show that its access to such sites in 5'-monophosphorylated RNA is hindered by obstacles-such as bound proteins or ribosomes or coaxial small RNA (sRNA) base pairing-that disrupt the path from the 5' end to those sites and prolong mRNA lifetimes. These findings suggest that RNase E searches for cleavage sites by scanning linearly from the 5'-terminal monophosphate along single-stranded regions of RNA and that its progress is impeded by structural discontinuities encountered along the way. This discovery has major implications for gene regulation in bacteria and suggests a general mechanism by which other prokaryotic and eukaryotic regulatory proteins can be controlled.
细菌细胞中 mRNA 寿命的多样性与 RNase E 的松弛切割位点特异性难以协调，RNase E 是对控制 mRNA 降解最重要的内切核酸酶。该酶通常被认为通过在三维空间中自由搜索来定位切割位点。然而，我们的结果现在表明，其对 5'-单磷酸化 RNA 中这些位点的访问受到障碍的阻碍，例如结合蛋白或核糖体或共轴小 RNA（sRNA）碱基配对，这些障碍会破坏从 5' 端到这些位点的路径并延长 mRNA 的寿命。这些发现表明，RNase E 通过从 5'-末端单磷酸沿着 RNA 的单链区域线性扫描来寻找切割位点，并且其进展受到沿途遇到的结构不连续性的阻碍。这一发现对细菌中的基因调控具有重大意义，并暗示了其他原核和真核调节蛋白可以被控制的一般机制。
