Interaction of the La-related protein Slf1 with colliding ribosomes maintains translation of oxidative-stress responsive mRNAs.
Interaction of the La-related protein Slf1 with colliding ribosomes maintains translation of oxidative-stress responsive mRNAs.
复制标题
DOI：
10.1093/nar/gkad272
复制
发表时间：
2023-06-23
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
为了应对氧化应激，细胞重新编程基因表达，以提高抗氧化酶水平，促进生存。在酿酒酵母中，多聚体相互作用的La相关蛋白(LARPs)SLF1和Sro9以未知的方式帮助蛋白质合成适应胁迫。为了深入了解它们在应激反应中的作用机制，我们测定了应激和非应激细胞中LARP mRNA的结合位置。在最佳和应激条件下，这两种蛋白质都结合在应激调节抗氧化酶和其他高度翻译的mRNAs的编码区。LAP相互作用部位被核糖体足迹所包围并丰富，这表明已经确定了核糖体-LARP-mRNA复合体。尽管在SLF1Δ中，应激诱导的抗氧化酶mRNAs的翻译被减弱，但这些mRNAs仍然存在于多聚体上。进一步聚焦于SLF1，我们发现它在核糖核酸酶处理后既能与单体结合，又能与双体结合。SLF1Δ减少了应激过程中二体的聚集，并改变了程序性核糖体的移码速率。我们认为SLF1是一个核糖体相关的翻译调节器，它稳定停滞/碰撞的核糖体，防止核糖体移码，从而促进一组高翻译的mRNAs的翻译，这些mRNAs共同促进细胞生存和适应应激。LARP SLF1稳定核糖体，翻译抗氧化酶mRNAs，促进细胞对压力的适应。
In response to oxidative stress cells reprogram gene expression to enhance levels of antioxidant enzymes and promote survival. In Saccharomyces cerevisiae the polysome-interacting La-related proteins (LARPs) Slf1 and Sro9 aid adaptation of protein synthesis during stress by undetermined means. To gain insight in their mechanisms of action in stress responses, we determined LARP mRNA binding positions in stressed and unstressed cells. Both proteins bind within coding regions of stress-regulated antioxidant enzyme and other highly translated mRNAs in both optimal and stressed conditions. LARP interaction sites are framed and enriched with ribosome footprints suggesting ribosome–LARP–mRNA complexes are identified. Although stress-induced translation of antioxidant enzyme mRNAs is attenuated in slf1Δ, these mRNAs remain on polysomes. Focusing further on Slf1, we find it binds to both monosomes and disomes following RNase treatment. slf1Δ reduces disome enrichment during stress and alters programmed ribosome frameshifting rates. We propose that Slf1 is a ribosome-associated translational modulator that stabilises stalled/collided ribosomes, prevents ribosome frameshifting and so promotes translation of a set of highly-translated mRNAs that together facilitate cell survival and adaptation to stress. LaRP Slf1 stabilises ribosomes translating antioxidant enzyme mRNAs to promote cellular adaptation to stress.
登录
查看更多内容
影响因子：
16
作者：
D'Orazio KN;Green R
通讯作者：
Green R
影响因子：
12.3
作者：
Castel SE;Levy-Moonshine A;Mohammadi P;Banks E;Lappalainen T
通讯作者：
Lappalainen T
DOI：
10.1261/rna.078964.121
发表时间：
2022-03
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Houston L;Platten EM;Connelly SM;Wang J;Grayhack EJ
通讯作者：
Grayhack EJ
影响因子：
7.2
作者：
Dever TE;Dinman JD;Green R
通讯作者：
Green R
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T