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View Article and Find Full Text PDFThe current vaccine against tuberculosis, live attenuated Mycobacterium bovis BCG, has variable efficacy, but development of an effective alternative is severely hampered by the lack of an immune correlate of protection. There has been a recent resurgence of interest in functional in vitro mycobacterial growth inhibition assays (MGIAs), which provide a measure of a range of different immune mechanisms and their interactions. We identified a positive correlation between mean corpuscular haemoglobin and in vitro growth of BCG in whole blood from healthy UK human volunteers.
View Article and Find Full Text PDFOligomeric complexes of Trax and Translin proteins, known as C3POs, participate in several eukaryotic nucleic acid metabolism pathways, including RNA interference and tRNA processing. In RNA interference in humans and Drosophila, C3PO activates the RNA-induced silencing complex (RISC) by removing the passenger strand of the small interfering RNA precursor duplex, using nuclease activity present in Trax. How C3POs engage with nucleic acid substrates is unknown.
View Article and Find Full Text PDFMeristems of seed plants continuously produce new cells for incorporation into maturing tissues. A tightly controlled balance between cell proliferation in the center and cell differentiation at the periphery of the shoot meristem maintains its integrity. Here, we describe the role of three GRAS genes, named LOST MERISTEMS genes, in shoot apical meristem maintenance and axillary meristem formation.
View Article and Find Full Text PDFTarget recognition in RNA silencing is governed by the "seed sequence" of a guide RNA strand associated with the PIWI/MID domain of an Argonaute protein in RISC. Using a reconstituted in vitro target recognition system, we show that a model PIWI/MID domain protein confers position-dependent tightening and loosening of guide-strand-target interactions. Over the seed sequence, the interaction affinity is enhanced up to approximately 300-fold.
View Article and Find Full Text PDFIn plants, worms, and fungi, RNA-dependent RNA polymerases (RDRs) amplify the production of short-interfering RNAs (siRNAs) that mediate RNA silencing. In Arabidopsis, RDR6 is thought to copy endogenous and exogenous RNA templates into double-stranded RNAs (dsRNAs), which are subsequently processed into siRNAs by one or several of the four Dicer-like enzymes (DCL1-->4). This reaction produces secondary siRNAs corresponding to sequences outside the primary targeted regions of a transcript, a phenomenon called transitivity.
View Article and Find Full Text PDFWe show, with miR171, that plant miRNA genes are modular independent transcription units in which the fold-back pre-miRNA is sufficient for miRNA processing, and that the upstream region contains highly specific promoter elements. Processing depends on flanking sequences within the miRNA stem-loop precursor rather than the miRNA sequence itself, and mutations affecting target pairing at the center and 5' but not 3' region of the miRNA compromise its function in vivo. Inactivation of the SDE1 RNA-dependent-RNA-polymerase was mandatory for accurate representation of miRNA activity by sensor constructs in Arabidopsis.
View Article and Find Full Text PDFIn plants, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are effectors of RNA silencing, a process involved in defense through RNA interference (RNAi) and in development. Plant viruses are natural targets of RNA silencing, and as a counterdefensive strategy, they have evolved highly diverse silencing suppressor proteins. Although viral suppressors are usually thought to act at distinct steps of the silencing machinery, there had been no consensus system so far that allowed a strict side-by-side analysis of those factors.
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