Cell reports | Yao Chengguo of our hospital and Ye Congting of Xiamen University report on the new universal function of the core splicing complex in maintaining full-length mRNA transcription

The classical molecular biological function of the five pre-mRNA splicing core snRNP complexes (U1, U2, U4, U5, U6) is the pre-mRNA splicing function of eukaryotes described in biochemistry textbooks. In 2024, Yao's research group and Ye Congting's research group from Xiamen University published a paper in the internationally renowned journal PNAS, reporting that U4 snRNP, like U1 snRNP, can prematurely terminate transcriptome inhibition. To maintain the integrity of the total length of the pre - mRNA transcription universality new features (https://pubmed.ncbi.nlm.nih.gov/38917004/), but other core snRNP whether also have the same new features, is not very clear. In view of the universality of pre-mRNA splicing core snRNP in eukaryotic cells and the wide range of influencing genes, it is an important issue in the current research on the molecular mechanism of mRNA co-transcription processing to explore whether other splicing core snRNP has similar functions. On February 28, 2025, Yao Chengguo's research group from Stem Cell Center of our Hospital and Ye Congting's research group from Xiamen University published a paper entitled "Functional inhibition of core spliceosomal machinery activates intronic" in Cell Reports premature cleavage and polyadenylation of pre-mRNAs "paper reports the latest research results on this key problem in the field. This is another important progress in the field of mRNA length regulation by this research group in recent years (2017, NAR; 2018,2019,2021,2022, RNA Biol.,2023 JBC; 2024 PNAS). They designed an antisense morpholino oligonucleotide (AMO) for U6 snRNP and U2 snRNP, which were transferred into conventional cell lines (HeLa, HEK-293, NIH-3T3, etc.) through in vitro biochemistry. In RNA in situ hybridization and other experiments, they determined that these AMO can specifically inhibit the function of snRNP. They then extracted total RNA from the cells and performed mRNA 3 '-seq. The results confirmed the previous conjecture that U6 snRNP and U2 snRNP, like U1 snRNP and U4 snRNP previously reported, can inhibit premature 3 'terminal processing (PCPA, premature cleavage and polyadenylation) at transcriptome scale. Corresponding to this result, further RNAPII Chain-SEQ experiments also showed that U6 and U2 could prevent premature transcription termination (PTT) by transcriptome size. It is worth mentioning that U1/U2/U4/U6, in addition to inhibiting premature 3 'end processing in introns at the transcriptome scale, can also inhibit premature 3' end processing in the 3 'untranslated region (3' -UTR) of some genes. In summary, this study updates the field's understanding of the function of the mRNA core splicing complex. Together with the published PNAS papers of our research group, this Cell Reports systematically reported that U1/U2/U4/U6 can prevent PCPA/PTT in the process of gene transcription at the transcriptome scale, so as to maintain full-length pre-mRNA expression. Corrects a series of misleading claims published since 2010 by the Gideon Dreyfuss Laboratory about this new function unique to U1 snRNP (2010, Nature; 2012, Cell;  2017, NSMB;  2019, Mol Cell). The results of this systematic study suggest that pre-mRNA splicing may universally inhibit new functions of PCPA/PTT, thus adding new content to gene expression regulation under the central rule of eukaryotic molecular biology.

  Graduate students Feng Qiumin and Li Mengzhao, graduate students Lin Zejin and Zhao Danhui from Xiamen University are the co-first authors of the paper, Associate Professor Ye Congting from Xiamen University is the co-corresponding author, and Associate Professor Yao Chengguo from Xiamen University is the final corresponding author. The research was supported by several grants, including the National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province.