Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado, USA.
Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado, USA; Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
J Biol Chem. 2023 Sep;299(9):105139. doi: 10.1016/j.jbc.2023.105139. Epub 2023 Aug 6.
The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves the addition of oligo(A) tails by non-canonical poly(A) polymerases, which then recruit processive sequence-independent 3' to 5' exonucleases for RNA degradation. This pathway of decay is also regulated by three 3' to 5' exoribonucleases, USB1, PARN, and TOE1, which remove oligo(A) tails and thereby can protect ncRNAs from decay in a manner analogous to the deubiquitination of proteins. Loss-of-function mutations in these genes lead to premature degradation of some ncRNAs and lead to specific human diseases such as Poikiloderma with Neutropenia (PN) for USB1, Dyskeratosis Congenita (DC) for PARN and Pontocerebellar Hypoplasia type 7 (PCH7) for TOE1. Herein, we review the biochemical properties of USB1, PARN, and TOE1, how they modulate ncRNA levels, and their roles in human diseases.
非编码 RNA（ncRNA）的水平受到转录、RNA 加工和 RNA 降解途径的调节。ncRNA 降解的一种机制涉及非典型 poly(A) 聚合酶添加寡聚（A）尾巴，然后招募进行性序列非依赖性 3' 到 5' 核酸外切酶进行 RNA 降解。这种衰变途径还受三个 3' 到 5' 的核酸外切酶 USB1、PARN 和 TOE1 调节，它们去除寡聚（A）尾巴，从而可以防止 ncRNA 降解，类似于蛋白质的去泛素化。这些基因的功能丧失突变导致一些 ncRNA 的过早降解，并导致特定的人类疾病，如 USB1 的中性粒细胞减少性斑状皮肤病（PN）、PARN 的先天性角化不良症（DC）和 TOE1 的桥小脑发育不良 7 型（PCH7）。本文综述了 USB1、PARN 和 TOE1 的生化特性，它们如何调节 ncRNA 水平以及它们在人类疾病中的作用。
