A newly identified Leishmania IF4E-interacting protein, Leish4E-IP2, modulates the activity of cap-binding protein paralogs

Nitin Tupperwar, Shimi Meleppattu, Rohit Shrivastava, Nofar Baron, Ayelet Gilad, Gerhard Wagner, Mélissa Léger-Abraham, Michal Shapira

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the preinitiation complex at the 5 end of mRNAs and regulates translation initiation. The requirement of Leishmania to survive in changing environments can explain why they encode multiple eIF4E (LeishIF4Es) and eIF4G (LeishIF4Gs) paralogs, as each could be assigned a discrete role during their life cycle. Here we show that the expression and activity of different LeishIF4Es change during the growth of cultured promastigotes, urging a search for regulatory proteins. We describe a novel LeishIF4E-interacting protein, Leish4E-IP2, which contains a conserved Y(X)4L IF4E-binding-motif. Despite its capacity to bind several LeishIF4Es, Leish4E-IP2 was not detected in m7GTP-eluted cap-binding complexes, suggesting that it could inhibit the cap-binding activity of LeishIF4Es. Using a functional assay, we show that a recombinant form of Leish4E-IP2 inhibits the cap-binding activity of LeishIF4E-1 and LeishIF4E-3. Furthermore, we show that transgenic parasites expressing a tagged version of Leish4E-IP2 also display reduced cap-binding activities of tested LeishIF4Es, and decreased global translation. Given its ability to bind more than a single LeishIF4E, we suggest that Leish4E-IP2 could serve as a broad-range repressor of Leishmania protein synthesis.

Original languageEnglish
Pages (from-to)4405-4417
Number of pages13
JournalNucleic Acids Research
Volume48
Issue number8
DOIs
StatePublished - 1 Jan 2020

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'A newly identified Leishmania IF4E-interacting protein, Leish4E-IP2, modulates the activity of cap-binding protein paralogs'. Together they form a unique fingerprint.

Cite this