TY - JOUR
T1 - LeishIF3d is a non-canonical cap-binding protein in Leishmania
AU - Bose, Priyanka
AU - Baron, Nofar
AU - Pullaiahgari, Durgeshwar
AU - Ben-Zvi, Anat
AU - Shapira, Michal
N1 - Funding Information:
This work was supported by grants from the Israel Science Foundation (471/21, 333/17) and from the Deutche Forschungsgemeinschaft with Dieter Wolf (WO 1579/3-1). PB is supported by the Kreitman School fellowship.
Publisher Copyright:
Copyright © 2023 Bose, Baron, Pullaiahgari, Ben-Zvi and Shapira.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the pre-initiation complex at the 5′ end of mRNAs driving translation initiation. The genome of Leishmania encodes a large repertoire of cap-binding complexes that fulfill a variety of functions possibly involved in survival along the life cycle. However, most of these complexes function in the promastigote life form that resides in the sand fly vector and decrease their activity in amastigotes, the mammalian life form. Here we examined the possibility that LeishIF3d drives translation in Leishmania using alternative pathways. We describe a non-canonical cap-binding activity of LeishIF3d and examine its potential role in driving translation. LeishIF3d is required for translation, as reducing its expression by a hemizygous deletion reduces the translation activity of the LeishIF3d(+/−) mutant cells. Proteomic analysis of the mutant cells highlights the reduced expression of flagellar and cytoskeletal proteins, as reflected in the morphological changes observed in the mutant cells. Targeted mutations in two predicted alpha helices diminish the cap-binding activity of LeishIF3d. Overall, LeishIF3d could serve as a driving force for alternative translation pathways, although it does not seem to offer an alternative pathway for translation in amastigotes.
AB - Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the pre-initiation complex at the 5′ end of mRNAs driving translation initiation. The genome of Leishmania encodes a large repertoire of cap-binding complexes that fulfill a variety of functions possibly involved in survival along the life cycle. However, most of these complexes function in the promastigote life form that resides in the sand fly vector and decrease their activity in amastigotes, the mammalian life form. Here we examined the possibility that LeishIF3d drives translation in Leishmania using alternative pathways. We describe a non-canonical cap-binding activity of LeishIF3d and examine its potential role in driving translation. LeishIF3d is required for translation, as reducing its expression by a hemizygous deletion reduces the translation activity of the LeishIF3d(+/−) mutant cells. Proteomic analysis of the mutant cells highlights the reduced expression of flagellar and cytoskeletal proteins, as reflected in the morphological changes observed in the mutant cells. Targeted mutations in two predicted alpha helices diminish the cap-binding activity of LeishIF3d. Overall, LeishIF3d could serve as a driving force for alternative translation pathways, although it does not seem to offer an alternative pathway for translation in amastigotes.
KW - LeishIF3d
KW - Leishmania
KW - cap-binding activity
KW - translation
KW - trypanosomatids
UR - http://www.scopus.com/inward/record.url?scp=85161977185&partnerID=8YFLogxK
U2 - 10.3389/fmolb.2023.1191934
DO - 10.3389/fmolb.2023.1191934
M3 - Article
C2 - 37325473
AN - SCOPUS:85161977185
SN - 2296-889X
VL - 10
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
M1 - 1191934
ER -