eIF3 engages with 3'-UTR termini of highly translated mRNAs in neural progenitor cells.
eIF3 engages with 3'-UTR termini of highly translated mRNAs in neural progenitor cells.
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eIF3 与神经祖细胞中高度翻译的 mRNA 的 3-UTR 末端结合。
DOI：
10.1101/2023.11.11.566681
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Cate,JamieHD
中科院分区：
文献类型：
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作者：
Mestre-Fos,Santi;Ferguson,Lucas;Trinidad,Marena;Ingolia,NicholasT;Cate,JamieHD
干细胞分化涉及蛋白质合成的全球增加，以满足专门细胞类型的需求。然而，这种翻译爆发的分子机制和起始因子的参与在很大程度上仍然未知。在这里，我们调查的作用，真核起始因子3（eIF 3）在人多能干细胞（hPSC）衍生的神经祖细胞（NPC）的早期分化。使用Quick-irCLIP和交替多聚腺苷酸化（阿帕）Seq，我们显示eIF 3主要与多个mRNA同种型的3'非翻译区（3'-UTR）末端交联，邻近poly（A）尾。此外，我们发现eIF 3在3 '-UTR末端的结合依赖于多聚腺苷酸化。在mRNA的3 '-UTR末端的高eIF 3交联与高翻译活性相关，如通过核糖体分析所确定的，但与翻译效率无关。本文提供的结果表明，eIF 3与高度翻译mRNA的3 '-UTR末端接合，这可能反映了eIF 3的一般而非特异性调节功能，并支持mRNA环化在mRNA翻译机制中的作用。
Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3’ untranslated region (3’-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3’-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3’-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling, but not with translational efficiency. The results presented here show that eIF3 engages with 3’-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation.