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Biology subjects

Ghezelbash, S.

Publications and source records attributed to Ghezelbash, S..

2 recordsLinked to original sources

ARHGEF3 Regulates Hair Follicle Morphogenesis

During embryogenesis, cells arrange into precise patterns that enable tissues and organs to develop specialized functions. Despite its critical importance, the molecular choreography behind these collective cellular behaviors remains elusive, posing a major challenge in developmental biology and limiting advances in regenerative medicine. By using the mouse hair follicle as a mini-organ system to study the formation of bud-like structures during embryonic development, our work uncovers a crucial role for the Rho GTPase regulator ARHGEF3 in hair follicle morphogenesis. We demonstrate that Arhgef3 expression is upregulated at the onset of hair follicle placode formation. In Arhgef3 knockout animals, we observed defects in placode compaction, leading to impaired hair follicle downgrowth. Through cell culture models, we show that ARHGEF3 promotes F-actin accumulation at the cell cortex and P-cadherin enrichment at cell-cell junctions. Collectively, our study identifies ARHGEF3 as a new regulator of cell shape rearrangements during hair placode morphogenesis, warranting further exploration of its role in other epithelial appendages that arise from similar developmental processes.

developmental biology↗

Location specific small RNA annealing to the HCV 5' UTR promotes Hepatitis C Virus replication by favoring IRES formation and stimulating virus translation

Hepatitis C virus (HCV) genome replication requires annealing of a liver specific small-RNA, miR-122 to 2 sites on 5 untranslated region (UTR). Annealing has been reported to a) stabilize the genome, b) promote translation, and c) induce the canonical HCV 5 UTR Internal Ribosome Entry Site (IRES) structure. In this report we identify the relative impact of small RNA annealing on the three functions ascribed to miR-122 and generate a mechanistic model for miR-122 promotion of HCV. First, we identified that perfectly complementary small RNAs that anneal to different locations on the HCV 5 UTR stimulate replication with varying efficiencies and mapped the region on the HCV genome to which small RNA annealing promotes virus replication. Second, by using a panel of small RNAs that promote with varying efficiencies we link HCV replication induction with translation stimulation and 5 UTR RNA structure modifications. However, replication promotion was not linked to genome stabilization since all small RNAs tested could stabilize the viral genome regardless of their ability to promote replication. Thus, we propose that miR-122 annealing promotes HCV replication primarily by activating the HCV IRES and stimulating translation, and that miR-122-induced HCV genome stabilization is insufficient alone but enhances virus replication. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/008417v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@178a857org.highwire.dtl.DTLVardef@741083org.highwire.dtl.DTLVardef@1e84743org.highwire.dtl.DTLVardef@9eadd2_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

microbiology↗