The RNA-associated proteins MKT1 and MKT1L form alternative PBP1-containing complexes in Trypanosoma brucei

• Verfasst von: Melo do Nascimento, Larissa [VerfasserIn]
• Verfasst von: Terrao, Monica [VerfasserIn]
• Verfasst von: Marucha, Kevin [VerfasserIn]
• Verfasst von: Liu, Bin [VerfasserIn]
• Verfasst von: Falk, Franziska [VerfasserIn]
• Verfasst von: Clayton, Christine [VerfasserIn]
• Titel: The RNA-associated proteins MKT1 and MKT1L form alternative PBP1-containing complexes in Trypanosoma brucei
• Verf.angabe: Larissa Melo do Nascimento, Monica Terrao, Kevin Kamanyi Marucha, Bin Liu, Franziska Egler, and Christine Clayton
• E-Jahr: 2020
• Jahr: June 12, 2020
• Umfang: 16 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 24.09.2020
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2020
• Band/Heft Quelle: 295(2020), 32, Seite 10940-10955
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.RA120.013306
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ataxia telangiectasia
• Sach-SW: ataxin-2
• Sach-SW: eukaryotic translation initiation factor 4E (eIF4E)
• Sach-SW: eukaryotic translation initiation factor 4G (eIF4G)
• Sach-SW: MKT1
• Sach-SW: mRNA
• Sach-SW: ribonuclear protein (RNP)
• Sach-SW: Trypanosoma brucei
• K10plus-PPN: 1733681949

Abstract

Control of gene expression in kinetoplastids such as trypanosomes depends heavily on RNA-binding proteins that influence mRNA decay and translation. We previously showed that the trypanosome protein MKT1 forms a multicomponent protein complex: MKT1 interacts with PBP1, which in turn recruits LSM12 and poly(A)-binding protein. MKT1 is recruited to mRNAs by sequence-specific RNA-binding proteins, resulting in stabilization of the bound mRNA. We here show that PBP1, LSM12, and a 117-residue protein, XAC1 (Tb927.7.2780), are present in complexes that contain either MKT1 or an MKT1-like protein, MKT1L (Tb927.10.1490). All five proteins are present predominantly in the complexes, and we found evidence for a minor subset of complexes containing both MKT1 and MKT1L. XAC1-containing complexes reproducibly contained RNA-binding proteins that were previously found associated with MKT1. Moreover, XAC1- or MKT1-containing complexes specifically recruited one of the two poly(A)-binding proteins, PABP2, and one of the six cap-binding translation initiation complexes, EIF4E6-EIF4G5. Yeast two-hybrid assay results indicated that MKT1 directly interacts with EIF4G5. MKT1-PBP1 complexes can therefore interact with mRNAs via their poly(A) tails and caps, as well as through sequence-specific RNA-binding proteins. Correspondingly, MKT1 is associated with many mRNAs, although not with those encoding ribosomal proteins. Meanwhile, MKT1L resembles MKT1 at the C terminus but additionally features an N-terminal extension with low-complexity regions. Although MKT1L depletion inhibited cell proliferation, we found no evidence that it specifically interacts with RNA-binding proteins or mRNA. We speculate that MKT1L may compete with MKT1 for PBP1 binding and thereby modulate the function of MKT1-containing complexes.