Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, D-37075 Göttingen, Germany.
NGS-Serviceeinrichtung für Integrative Genomik (NIG), Institut für Humangenetik, Universitätsmedizin Göttingen, D-37075 Göttingen, Germany.
Nucleic Acids Res. 2023 Sep 8;51(16):8758-8773. doi: 10.1093/nar/gkad530.
CF IB/Hrp1 is part of the cleavage and polyadenylation factor (CPF) and cleavage factor (CF) complex (CPF-CF), which is responsible for 3' cleavage and maturation of pre-mRNAs. Although Hrp1 supports this process, its presence is not essential for the cleavage event. Here, we show that the main function of Hrp1 in the CPF-CF complex is the nuclear mRNA quality control of proper 3' cleavage. As such, Hrp1 acts as a nuclear mRNA retention factor that hinders transcripts from leaving the nucleus until processing is completed. Only after proper 3' cleavage, which is sensed through contacting Rna14, Hrp1 recruits the export receptor Mex67, allowing nuclear export. Consequently, its absence results in the leakage of elongated mRNAs into the cytoplasm. If cleavage is defective, the presence of Hrp1 on the mRNA retains these elongated transcripts until they are eliminated by the nuclear exosome. Together, we identify Hrp1 as the key quality control factor for 3' cleavage.
CF IB/Hrp1 是切割多聚腺苷酸化因子（CPF）和切割因子（CF）复合物（CPF-CF）的一部分，负责前体 mRNA 的 3' 切割和成熟。虽然 Hrp1 支持这一过程，但它的存在对于切割事件并不是必需的。在这里，我们表明 Hrp1 在 CPF-CF 复合物中的主要功能是核 mRNA 的质量控制，以确保正确的 3' 切割。因此，Hrp1 作为一种核 mRNA 滞留因子，阻止转录本离开细胞核，直到处理完成。只有在通过与 Rna14 接触感知到适当的 3' 切割后，Hrp1 才会招募输出受体 Mex67，允许核输出。因此，如果 Hrp1 缺失，就会导致延长的 mRNA 泄漏到细胞质中。如果切割有缺陷，mRNA 上 Hrp1 的存在会保留这些延长的转录本，直到它们被核 exosome 消除。总之，我们将 Hrp1 确定为 3' 切割的关键质量控制因子。
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