Publications by authors named "Katrin Heindl"

4 Publications

  • Page 1 of 1

The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells.

EMBO J 2014 Dec 6;33(24):2922-36. Epub 2014 Nov 6.

Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria

The unfolded protein response (UPR) is a conserved stress-signaling pathway activated after accumulation of unfolded proteins within the endoplasmic reticulum (ER). Active UPR signaling leads to unconventional, enzymatic splicing of XBP1 mRNA enabling expression of the transcription factor XBP1s to control ER homeostasis. While IRE1 has been identified as the endoribonuclease required for cleavage of this mRNA, the corresponding ligase in mammalian cells has remained elusive. Here, we report that RTCB, the catalytic subunit of the tRNA ligase complex, and its co-factor archease mediate XBP1 mRNA splicing both in vitro and in vivo. Depletion of RTCB in plasma cells of Rtcb(fl/fl) Cd23-Cre mice prevents XBP1s expression, which normally is strongly induced during plasma cell development. RTCB-depleted plasma cells show reduced and disorganized ER structures as well as severe defects in antibody secretion. Targeting RTCB and/or archease thus represents a promising strategy for the treatment of a growing number of diseases associated with elevated expression of XBP1s.
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http://dx.doi.org/10.15252/embj.201490332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282640PMC
December 2014

Nol9 is a novel polynucleotide 5'-kinase involved in ribosomal RNA processing.

EMBO J 2010 Dec 9;29(24):4161-71. Epub 2010 Nov 9.

IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

In a cell, an enormous amount of energy is channelled into the biogenesis of ribosomal RNAs (rRNAs). In a multistep process involving a large variety of ribosomal and non-ribosomal proteins, mature rRNAs are generated from a long polycistronic precursor. Here, we show that the non-ribosomal protein Nol9 is a polynucleotide 5'-kinase that sediments primarily with the pre-60S ribosomal particles in HeLa nuclear extracts. Depletion of Nol9 leads to a severe impairment of ribosome biogenesis. In particular, the polynucleotide kinase activity of Nol9 is required for efficient generation of the 5.8S and 28S rRNAs from the 32S precursor. Upon Nol9 knockdown, we also observe a specific maturation defect at the 5' end of the predominant 5.8S short-form rRNA (5.8S(S)), possibly due to the Nol9 requirement for 5'>3' exonucleolytic trimming. In contrast, the endonuclease-dependent generation of the 5'-extended, minor 5.8S long-form rRNA (5.8S(L)) is largely unaffected. This is the first report of a nucleolar polynucleotide kinase with a role in rRNA processing.
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http://dx.doi.org/10.1038/emboj.2010.275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018789PMC
December 2010

Role of the RNA/DNA kinase Grc3 in transcription termination by RNA polymerase I.

EMBO Rep 2010 Oct 3;11(10):758-64. Epub 2010 Sep 3.

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.

Transcription termination by RNA polymerase I in Saccharomyces cerevisiae is mediated by a 'torpedo' mechanism: co-transcriptional RNA cleavage by Rnt1 at the ribosomal DNA 3'-region generates a 5'-end that is recognized by the 5'-3' exonuclease Rat1; this degrades the downstream transcript and eventually causes termination. In this study, we identify Grc3 as a new factor involved in this process. We demonstrate that GRC3, an essential gene of previously unknown function, encodes a polynucleotide kinase that is required for efficient termination by RNA polymerase I. We propose that it controls the phosphorylation status of the downstream Rnt1 cleavage product and thereby regulates its accessibility to the torpedo Rat1.
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http://dx.doi.org/10.1038/embor.2010.130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948184PMC
October 2010

Small RNAs and their big implications: in vivo, in vitro, in silico.

RNA Biol 2007 Nov;4(3):165-8

Institue of Molecular Biology, Vienna, Austria.

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http://dx.doi.org/10.4161/rna.4.3.5309DOI Listing
November 2007