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1.
Cell Rep ; 42(10): 113283, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37862172

ABSTRACT

Cells activate stress response pathways to survive adverse conditions. Such responses involve the inhibition of global cap-dependent translation. This inhibition is a block that essential transcripts must escape via alternative methods of translation initiation, e.g., an internal ribosome entry site (IRES). IRESs have distinct structures and generally require a limited repertoire of translation factors. Cellular IRESs have been identified in many critical cellular stress response transcripts. We previously identified cellular IRESs in the murine insulin receptor (Insr) and insulin-like growth factor 1 receptor (Igf1r) transcripts and demonstrated their resistance to eukaryotic initiation factor 4F (eIF4F) inhibition. Here, we find that eIF5B preferentially promotes Insr, Igf1r, and hepatitis C virus IRES activity through a non-canonical mechanism that requires its highly charged and disordered N terminus. We find that the N-terminal region of eIF5B can drive cytoplasmic granule formation. This eIF5B granule is triggered by cellular stress and is sufficient to specifically promote IRES activity.


Subject(s)
Hepatitis C , Internal Ribosome Entry Sites , Animals , Mice , Eukaryotic Initiation Factors/genetics , Eukaryotic Initiation Factors/metabolism , Eukaryotic Initiation Factor-4F/metabolism , Protein Biosynthesis
2.
Mol Cell Biol ; 43(10): 485-499, 2023.
Article in English | MEDLINE | ID: mdl-37724583

ABSTRACT

IRES mediated translation initiation requires a different repertoire of factors than canonical cap-dependent translation. Treatments that inhibit the canonical translation factor EIF4G1 have little or no effect on the ability of the Insr and Igf1r cellular IRESes to promote translation. Transcripts for two cellular receptors contain RNA elements that facilitate translation initiation without intact EIF4G1. Cellular IRES mechanisms may resemble viral type III IRESes allowing them to promote translate with a limited number of initiation factors allowing them to work under stress conditions when canonical translation is repressed.


Subject(s)
Insulin-Like Peptides , Protein Biosynthesis , 5' Untranslated Regions/genetics , Ribosomes/metabolism , Eukaryotic Initiation Factor-4G/genetics , Eukaryotic Initiation Factor-4G/metabolism , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Receptors, Somatomedin/metabolism , RNA, Viral/metabolism
3.
Microbiol Resour Announc ; 9(45)2020 Nov 05.
Article in English | MEDLINE | ID: mdl-33154018

ABSTRACT

Vibrio natriegens, a fast-growing Gram-negative bacterium, is gaining interest as a platform for rapid biotechnology applications and metabolic engineering. Only a few bacteriophages that infect this bacterium have been identified. Here, we describe the isolation and characterization of two V. natriegens bacteriophages isolated from Hatches Creek, Wellfleet, Massachusetts.

4.
Elife ; 72018 10 23.
Article in English | MEDLINE | ID: mdl-30351272

ABSTRACT

Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active capping state. Knockdowns of Twinfilin and CP each cause similar defects in cell morphology, and elevated Twinfilin expression rescues defects caused by CARMIL hyperactivity. Together, these observations define Twinfilin as the first 'pro-capping' ligand of CP and lead us to propose important revisions to our understanding of the CP regulatory cycle.


Subject(s)
Actin Capping Proteins/metabolism , Gene Expression Regulation , Microfilament Proteins/metabolism , Animals , Binding Sites , Cell Line , Mice , Protein Binding , Protein Interaction Mapping
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