Pf SR1 controls alternative splicing and steady-state RNA levels in P lasmodium falciparum through preferential recognition of specific RNA motifs.

Autor: Eshar, Shiri, Altenhofen, Lindsey, Rabner, Alona, Ross, Phil, Fastman, Yair, Mandel‐Gutfreund, Yael, Karni, Rotem, Llinás, Manuel, Dzikowski, Ron
Předmět:
Zdroj: Molecular Microbiology; Jun2015, Vol. 96 Issue 6, p1283-1297, 15p, 1 Color Photograph, 3 Diagrams, 3 Graphs
Abstrakt: P lasmodium 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 Pf SR1 as a bona fide Ser/ Arg-rich ( SR) protein that shuttles between the nucleus and cytoplasm and regulates AS in P lasmodium falciparum. Here we show that Pf SR1 is localized adjacent to the Nuclear Pore Complex ( NPC) clusters in the nucleus of early stage parasites. To identify the endogenous RNA targets of Pf SR1, we adapted an inducible overexpression system for tagged Pf SR1 and performed RNA immunoprecipitation followed by microarray analysis ( RIP-chip) to recover and identify the endogenous RNA targets that bind Pf SR1. Bioinformatic analysis of these RNAs revealed common sequence motifs potentially recognized by Pf SR1. RNA- EMSAs show that Pf SR1 preferentially binds RNA molecules containing these motifs. Interestingly, we find that Pf SR1 not only regulates AS but also the steady-state levels of m RNAs containing these motifs in vivo. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index