Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, Göttingen 37077, Germany.
Nucleic Acids Res. 2022 Oct 28;50(19):11301-11314. doi: 10.1093/nar/gkac952.
Efficient gene expression requires properly matured mRNAs for functional transcript translation. Several factors including the guard proteins monitor maturation and act as nuclear retention factors for unprocessed pre-mRNAs. Here we show that the guard protein Npl3 monitors 5'-capping. In its absence, uncapped transcripts resist degradation, because the Rat1-Rai1 5'-end degradation factors are not efficiently recruited to these faulty transcripts. Importantly, in npl3Δ, these improperly capped transcripts escape this quality control checkpoint and leak into the cytoplasm. Our data suggest a model in which Npl3 associates with the Rai1 bound pre-mRNAs. In case the transcript was properly capped and is thus CBC (cap binding complex) bound, Rai1 dissociates from Npl3 allowing the export factor Mex67 to interact with this guard protein and support nuclear export. In case Npl3 does not detect proper capping through CBC attachment, Rai1 binding persists and Rat1 can join this 5'-complex to degrade the faulty transcript.
高效的基因表达需要成熟的 mRNA 来进行功能性转录翻译。几种因素，包括Guard 蛋白，监测 mRNA 的成熟过程，并作为未加工的前体 mRNA 的核保留因子。在这里，我们发现 Guard 蛋白 Npl3 可以监测 5' 加帽过程。在 Npl3 缺失的情况下，未加帽的转录本能够抵抗降解，因为 Rat1-Rai1 5' 端降解因子不能有效地被招募到这些错误的转录本上。重要的是，在 npl3Δ 中，这些不正确加帽的转录本逃避了这个质量控制检查点，并漏到细胞质中。我们的数据表明了一个模型，其中 Npl3 与 Rai1 结合的前体 mRNA 结合。如果转录本被正确加帽，从而与 CBC（帽结合复合物）结合，那么 Rai1 就会从 Npl3 上解离，从而允许出口因子 Mex67 与这种 Guard 蛋白相互作用，并支持核输出。如果 Npl3 没有通过 CBC 结合来检测到正确的加帽，那么 Rai1 的结合就会持续存在，并且 Rat1 可以加入这个 5' 复合物来降解有缺陷的转录本。
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