The group of Hans Spelbrink, theme Mitochondrial diseases, published a paper in Nucleic Acids Research, showing that two factors that are traditionally implicated in mitochondrial DNA replication, namely the mtDNA helicase Twinkle and the mtDNA single-stranded DNA-binding protein mtSSB, play an important role also in mitochondrial RNA metabolism.Publication: link.
Newly synthesized mitochondrial RNA is concentrated in structures juxtaposed to nucleoids, called RNA granules, that have been implicated in mitochondrial RNA processing and ribosome biogenesis. They showed that two classical mtDNA replication factors, the mtDNA helicase Twinkle and single-stranded DNA-binding protein mtSSB, contribute to RNA metabolism in mitochondria and to RNA granule biology. Twinkle colocalizes with both mitochondrial RNA granules and nucleoids, and it can serve as bait to greatly enrich established RNA granule proteins, such as G-rich sequence factor 1, GRSF1. Likewise, mtSSB also is not restricted to the nucleoids, and repression of either mtSSB or Twinkle alters mtRNA metabolism. Short-term Twinkle depletion greatly diminishes RNA granules but does not inhibit RNA synthesis or processing. Either mtSSB or GRSF1 depletion results in RNA processing defects, accumulation of mtRNA breakdown products as well as increased levels of dsRNA and RNA:DNA hybrids. In particular, the processing and degradation defects become more pronounced with both proteins depleted.
These findings suggest that Twinkle is essential for RNA organization in granules, and that mtSSB is involved in the recently proposed GRSF1-mtRNA degradosome pathway, a route suggested to be particularly aimed at degradation of G-quadruplex prone long non-coding mtRNAs.
Related news items
ERC Proof of Concept grant received by Ronald van Rij30 July 2020
Ronald van Rij, theme Infectious diseases and global health, received an ERC (European Research Council) Proof of Concept grant of 150,000 euros, in order to make arbovirus vaccines even safer.read more
Hypatia fellowship Call is open30 July 2020
The Hypatia fellowship round with the deadline 31 May has been canceled. Therefore, the next available deadline will be 27 September 2020. Radboudumc researchers are invited to scout young potentials to fill the strategic gaps within the research themes imbedded in RIHS and RIMLS.read more
Mihai Netea and colleagues published two papers back-to-back in The Journal of Clinical Investigation.29 July 2020
These back-to-back articles investigated the effect of BCG vaccination on trained immunity. The first article shows that BCG vaccination inhibits systemic inflammation, depending on gender. The second article demonstrates that the circadian rhythm influences the induction of trained immunity.read more
Genetic mutation reveals how coronavirus strikes TLR7 plays essential role in disease process28 July 2020
''Does a congenital immune defect play an important role in the defense against Coronavirus?'' This was published by Cas van der Made, Frank van der Veerdonk and Alexander Hoischen.read more
Summer greetings from René Bindels16 July 2020
In this last newsletter before most colleagues enjoy their well-deserved summer break, I would like to briefly summarize the first part of 2020 and look ahead to the many activities that will take place in the coming months of this unprecedented year.read more
Registration for Social Dutch course for researchers is open now14 July 2020
In October, a new course Social Dutch will start at Radboud In’to Languages. The course is very popular and we are happy to inform you that registrations for Social Dutch have been opened now!read more