title: PfSR1 controls alternative splicing and steady-state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs.
abstract: Plasmodium species have evolved complex biology to adapt to different hosts and changing environments throughout their life cycle. Remarkably, these adaptations are achieved by a relatively small genome. One way by which the parasite expands its proteome is through alternative splicing (AS). We recently identified PfSR1 as a bona fide Ser/Arg-rich (SR) protein that shuttles between the nucleus and cytoplasm and regulates AS in Plasmodium falciparum. Here we show that PfSR1 is localized adjacent to the Nuclear Pore Complex (NPC) clusters in the nucleus of early stage parasites. To identify the endogenous RNA targets of PfSR1, we adapted an inducible overexpression system for tagged PfSR1 and performed RNA immunoprecipitation followed by microarray analysis (RIP-chip) to recover and identify the endogenous RNA targets that bind PfSR1. Bioinformatic analysis of these RNAs revealed common sequence motifs potentially recognized by PfSR1. RNA-EMSAs show that PfSR1 preferentially binds RNA molecules containing these motifs. Interestingly, we find that PfSR1 not only regulates AS but also the steady-state levels of mRNAs containing these motifs in vivo.
authors: Department of Microbiology and Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Institute for Medical Research Israel-Canada, The Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors: Shiri
authors: S
authors: Eshar
authors: Department of Molecular Biology and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, 08544, USA.|Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, PA, 16802, USA.
authors: Lindsey
authors: L
authors: Altenhofen
authors: Department of Biology, Israel Institute of Technology-Technion, Haifa, Israel.
authors: Alona
authors: A
authors: Rabner
authors: Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, PA, 16802, USA.
authors: Phil
authors: P
authors: Ross
authors: Department of Microbiology and Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Institute for Medical Research Israel-Canada, The Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors: Yair
authors: Y
authors: Fastman
authors: Department of Biology, Israel Institute of Technology-Technion, Haifa, Israel.
authors: Yael
authors: Y
authors: Mandel-Gutfreund
authors: Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors: Rotem
authors: R
authors: Karni
authors: Department of Molecular Biology and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, 08544, USA.|Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, PA, 16802, USA.
authors: Manuel
authors: M
authors: Llinás
authors: Department of Microbiology and Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Institute for Medical Research Israel-Canada, The Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors: Ron
authors: R
authors: Dzikowski
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D059372:Nucleotide Motifs; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors