Surveillance of 3′ mRNA cleavage during transcription termination requires CF IB/Hrp1

Abstract

Abstract 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.