Project

Back to overview

Genetic and biochemical characterization of a ribosomal shunt.

Applicant Curran Joseph
Number 100221
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Molecular Biology
Start/End 01.04.2003 - 31.03.2007
Approved amount 306'120.00
Show all

All Disciplines (2)

Discipline
Molecular Biology
Genetics

Keywords (2)

translation initiation; ribosomal shunting

Lay Summary (English)

Lead
Lay summary
Sendai virus (SeV) is a prototype member of the Paramyxovirus family, a group of single stranded negative sense RNA viruses that includes the human pathogens measles virus and mumps virus. The labs work has focused on the expression of a series of viral non-structural proteins referred too as the “C-proteins” (C’, C Y1 and Y2). The term “non-structural” indicates that, although present in the infected cell, these proteins are not found in the viral particle. The “C-proteins” are not however essential for growth in cell culture, but play key roles in: (a) modulating the read-out from the viral genome, (b) maintenance of genomic stability, (c) viral particle budding, and, (d) modulating the host cell response during infection. With regards to the latter, these proteins target the innate arm of the immune system, namely the interferon response.All the C-proteins are expressed from a single messenger RNA (mRNA) which also encodes an essential viral protein called P (phosphoprotein). This P/C mRNA has therefore become a paradigm for expressional elasticity at the level of protein synthesis. We have demonstrated that:(1). The largest C’ protein initiates at the first start site and uses an unusual ACG initiation codon (these codons are normally AUG).(2). The P protein (second start site) and the C protein (third start site) are initiated on AUG codons via a process referred too as leaky scanning of the ribosome.(3). The shorter Y proteins arise in-vivo both by de-novo translation initiation (on the fourth and fifth start sites, both AUG codons) and by proteolytic processing of C’. This dual mode of expression, although unusual, is not unique in that it has been reported to occur on a cellular gene encoding a transcription factor (the CCAAT/enhancer binding protein b). Ribosomal access to these internal start sites is achieved by shunting, a mechanism in which the ribosome “jumps” from a region proximal to the mRNAs 5’ end (the initial site of entry onto the mRNA) to a region flanking the Y1/Y2 start sites. In this way, the start sites for C’, P and C are by-passed. Shunting may represent a means to ensure continued Y protein expression under conditions in which linear movement of the ribosome is compromised. This may have important consequences for viral infection since the host translational machinery is frequently a target for the cells anti-viral response. The nature of the intracellular proteinase that processes C’ remains elusive, although it can be mimicked in cell extracts using a number of proteinases. Results suggest that the C’ protein may serve as a Pro-protein whose role is to deliver the Y module to a specific intracellular site.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
57434 Genetic and biochemical characterization of a ribosomal shunt. 01.04.2000 Project funding (Div. I-III)

-