RBM17 Interacts with U2SURP and CHERP to Regulate Expression and Splicing of RNA-Processing Proteins
Antonia De Maio,
Hari Krishna Yalamanchili,
Carolyn J. Adamski,
Vincenzo A. Gennarino,
Zhandong Liu,
Jun Qin,
Sung Y. Jung,
Ronald Richman,
Harry Orr,
Huda Y. Zoghbi
Affiliations
Antonia De Maio
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA
Hari Krishna Yalamanchili
Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Carolyn J. Adamski
Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
Vincenzo A. Gennarino
Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Zhandong Liu
Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
Jun Qin
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Sung Y. Jung
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Ronald Richman
Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
Harry Orr
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
Huda Y. Zoghbi
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
Summary: RNA splicing entails the coordinated interaction of more than 150 proteins in the spliceosome, one of the most complex of the cell’s molecular machines. We previously discovered that the RNA-binding motif protein 17 (RBM17), a component of the spliceosome, is essential for survival and cell maintenance. Here, we find that it interacts with the spliceosomal factors U2SURP and CHERP and that they reciprocally regulate each other’s stability, both in mouse and in human cells. Individual knockdown of each of the three proteins induces overlapping changes in splicing and gene expression of transcripts enriched for RNA-processing factors. Our results elucidate the function of RBM17, U2SURP, and CHERP and link the activity of the spliceosome to the regulation of downstream RNA-binding proteins. These data support the hypothesis that, beyond driving constitutive splicing, spliceosomal factors can regulate alternative splicing of specific targets. : De Maio et al. find that the splicing factor RBM17 establishes a physical and functional relation with U2SURP and CHERP. Knockdown of these U2 snRNP-associated spliceosomal components reveals their synergistic activity toward regulation of a given set of transcripts rather than a more predictable transcriptome-wide inhibition of splicing. Keywords: RBM17, U2SURP, CHERP, splicing, spliceosome, RNA homeostasis, cryptic splicing
