Statistiques Relatives Aux Volontaires de Solidarité Internationales (VSI)

This report presents statistics related to international solidarity volunteering based on knowed volunteers

Distinct regions of RPB11 are required for heterodimerization with RPB3 in human and yeast RNA polymerase II

In Saccharomyces cerevisiae, RNA polymerase II assembly is probably initiated by the formation of the RPB3–RPB11 heterodimer. RPB3 is encoded by a single copy gene in the yeast, mouse and human genomes. The RPB11 gene is also unique in yeast and mouse, but in humans a gene family has been identified that potentially encodes several RPB11 proteins differing mainly in their C-terminal regions. We compared the abilities of both yeast and human proteins to heterodimerize. We show that the yeast RPB3/RPB11 heterodimer critically depends on the presence of the C-terminal region of RPB11. In contrast, the human heterodimer tolerates significant changes in RPB11 C-terminus, allowing two human RPB11 variants to heterodimerize with the same efficiency with RPB3. In keeping with this observation, the interactions between the conserved N-terminal ‘α-motifs’ is much more important for heterodimerization of the human subunits than for those in yeast. These data indicate that the heterodimerization interfaces have been modified during the course of evolution to allow a recent diversification of the human RPB11 subunits that remains compatible with heterodimerization with RPB3

A human RNA polymerase II subunit is encoded by a recently generated multigene family

BACKGROUND: The sequences encoding the yeast RNA polymerase II (RPB) subunits are single copy genes. RESULTS: While those characterized so far for the human (h) RPB are also unique, we show that hRPB subunit 11 (hRPB11) is encoded by a multigene family, mapping on chromosome 7 at loci p12, q11.23 and q22. We focused on two members of this family, hRPB11a and hRPB11b: the first encodes subunit hRPB11a, which represents the major RPB11 component of the mammalian RPB complex ; the second generates polypeptides hRPB11bα and hRPB11bβ through differential splicing of its transcript and shares homologies with components of the hPMS2L multigene family related to genes involved in mismatch-repair functions (MMR). Both hRPB11a and b genes are transcribed in all human tissues tested. Using an inter-species complementation assay, we show that only hRPB11bα is functional in yeast. In marked contrast, we found that the unique murine homolog of RPB11 gene maps on chromosome 5 (band G), and encodes a single polypeptide which is identical to subunit hRPB11a. CONCLUSIONS: The type hRPB11b gene appears to result from recent genomic recombination events in the evolution of primates, involving sequence elements related to the MMR apparatus

ETUDE DE L'ARN POLYMERASE II HUMAINE (CAS PARTICULIER DES SOUS-UNITES HRPB4 ET HRPB11)

STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts

International audienc

Interactions between the full complement of human RNA polymerase II subunits

AbstractAs an approach to elucidating the rules governing the assembly of human RNA polymerase II (hRPB), interactions between its subunits have been systematically analyzed. Eleven of the 12 expected hRPB subunits have previously been tested for reciprocal interactions (J. Biol. Chem. 272 (1997) 16815–16821). We now report the results obtained for the last subunit (hRPB4; Mol. Cell. Biol. 18 (1998) 1935–1945) and propose an essentially complete picture of the potential interactions occurring within hRPB. Finally, complementation experiments in yeast indicated that hRPB4 expression efficiently cured both heat and cold-sensitivity of RPB4-lacking strains, supporting the existence of conserved functional subunit interactions

OR10-002 - A novel TNFR1 transcript of TRAPS gene

International audienc

TNFR1-d2 carrying the p.(Thr79Met) pathogenic variant is a potential novel actor of TNFα/TNFR1 signalling regulation in the pathophysiology of TRAPS

International audienceBinding of tumour necrosis factor α (TNFα) to its receptor (TNFR1) is critical for both survival and death cellular pathways. TNFα/TNFR1 signalling is complex and tightly regulated at different levels to control cell fate decisions. Previously, we identified TNFR1-d2, an exon 2-spliced transcript of TNFRSF1A gene encoding TNFR1, whose splicing may be modulated by polymorphisms associated with inflammatory disorders. Here, we investigated the impact of TNFRSF1A variants involved in TNFR-associated periodic syndrome (TRAPS) on TNFR1-d2 protein expression and activity. We found that TNFR1-d2 could be translated by using an internal translation initiation codon and a de novo internal ribosome entry site (IRES), which resulted in a putative TNFR1 isoform lacking its N-terminal region. The kinetic of assembly of TNFR1-d2 clusters at the cell surface was reduced as compared with full-length TNFR1. Although co-localized with the full-length TNFR1, TNFR1-d2 neither activated nuclear factor (NF)-κB signalling, nor interfered with TNFR1-induced NF-κB activation. Translation of TNFR1-d2 carrying the severe p.(Thr79Met) pathogenic variant (also known as T50M) was initiated at the mutated codon, resulting in an elongated extracellular domain, increased speed to form preassembled clusters in absence of TNFα, and constitutive NF-κB activation. Overall, TNFR1-d2 might reflect the complexity of the TNFR1 signalling pathways and could be involved in TRAPS pathophysiology of patients carrying the p.(Thr79Met) disease-causing variant