PfSR1 controls alternative splicing and steady-state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs

Shiri Eshar, Lindsey Altenhofen, Alona Rabner, Phil Ross, Yair Fastman, Yael Mandel-Gutfreund, Rotem Karni, Manuel Llinas, Ron Dzikowski

Research output: Contribution to journalArticle

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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 fideSer/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.

Original languageEnglish (US)
Pages (from-to)1283-1297
Number of pages15
JournalMolecular Microbiology
Volume96
Issue number6
DOIs
StatePublished - Jan 1 2015

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Alternative Splicing
Plasmodium falciparum
RNA
Parasites
Nuclear Pore
Plasmodium
Proteome
Microarray Analysis
Life Cycle Stages
Computational Biology
Immunoprecipitation
RNA Recognition Motif
Cytoplasm
Genome
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Eshar, Shiri ; Altenhofen, Lindsey ; Rabner, Alona ; Ross, Phil ; Fastman, Yair ; Mandel-Gutfreund, Yael ; Karni, Rotem ; Llinas, Manuel ; Dzikowski, Ron. / PfSR1 controls alternative splicing and steady-state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs. In: Molecular Microbiology. 2015 ; Vol. 96, No. 6. pp. 1283-1297.
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Eshar, S, Altenhofen, L, Rabner, A, Ross, P, Fastman, Y, Mandel-Gutfreund, Y, Karni, R, Llinas, M & Dzikowski, R 2015, 'PfSR1 controls alternative splicing and steady-state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs', Molecular Microbiology, vol. 96, no. 6, pp. 1283-1297. https://doi.org/10.1111/mmi.13007

PfSR1 controls alternative splicing and steady-state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs. / Eshar, Shiri; Altenhofen, Lindsey; Rabner, Alona; Ross, Phil; Fastman, Yair; Mandel-Gutfreund, Yael; Karni, Rotem; Llinas, Manuel; Dzikowski, Ron.

In: Molecular Microbiology, Vol. 96, No. 6, 01.01.2015, p. 1283-1297.

Research output: Contribution to journalArticle

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AU - Eshar, Shiri

AU - Altenhofen, Lindsey

AU - Rabner, Alona

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AU - Fastman, Yair

AU - Mandel-Gutfreund, Yael

AU - Karni, Rotem

AU - Llinas, Manuel

AU - Dzikowski, Ron

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