Department of Interventional Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
Curr Genet. 2021 Apr;67(2):195-206. doi: 10.1007/s00294-020-01132-5. Epub 2020 Nov 26.
Gene transcription is a complex biological process that involves a set of factors, enzymes and nucleotides. Ssu72 plays a crucial role in every step of gene transcription. RNA polymerase II (RNAPII) occupies an important position in the synthesis of mRNAs. The largest subunit of RNAPII, Rpb1, harbors its C-terminal domain (CTD), which participates in the initiation, elongation and termination of transcription. The CTD consists of heptad repeats of the consensus motif Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 and is highly conserved among different species. The CTD is flexible in structure and undergoes conformational changes in response to serine phosphorylation and proline isomerization, which are regulated by specific kinases/phosphatases and isomerases, respectively. Ssu72 is a CTD phosphatase with catalytic activity against phosphorylated Ser5 and Ser7. The isomerization of Pro6 affects the binding of Ssu72 to its substrate. Ssu72 can also indirectly change the phosphorylation status of Ser2. In addition, Ssu72 is a member of the 3'-end cleavage and polyadenylation factor (CPF) complex. Together with other CPF components, Ssu72 regulates the 3'-end processing of premature mRNA. Recent studies have revealed other roles of Ssu72, including its roles in balancing phosphate homeostasis and controlling chromosome behaviors, which should be further explored. In conclusion, the protein Ssu72 is an enzyme worthy of attention, not confined to its role in gene transcription.
基因转录是一个复杂的生物学过程，涉及一系列的因素、酶和核苷酸。Ssu72 在基因转录的每一步中都起着至关重要的作用。RNA 聚合酶 II（RNAPII）在 mRNA 的合成中占据重要地位。RNAPII 的大亚基 Rpb1 含有其 C 端结构域（CTD），参与转录的起始、延伸和终止。CTD 由七肽重复的保守基序 Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 组成，在不同物种中高度保守。CTD 结构灵活，可根据丝氨酸磷酸化和脯氨酸异构化进行构象变化，分别由特定的激酶/磷酸酶和异构酶调节。Ssu72 是一种 CTD 磷酸酶，对磷酸化的 Ser5 和 Ser7 具有催化活性。Pro6 的异构化影响 Ssu72 与其底物的结合。Ssu72 还可以间接改变 Ser2 的磷酸化状态。此外，Ssu72 是 3'-末端切割和多聚腺苷酸化因子（CPF）复合物的成员。与其他 CPF 成分一起，Ssu72 调节前体 mRNA 的 3'-末端加工。最近的研究揭示了 Ssu72 的其他作用，包括在平衡磷酸盐稳态和控制染色体行为方面的作用，这些作用需要进一步探索。总之，Ssu72 蛋白是一种值得关注的酶，不仅限于其在基因转录中的作用。
