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.
Want to know more about these subjects? Click on the buttons below for more news.
RIMLSRIHSHealthcare improvement scienceIQ healthcareResearchCancer development and immune defenseRare cancersTumors of the digestive tract Urological cancersWomen's cancersInfectious diseases and global healthInflammatory diseases Mitochondrial diseasesReconstructive and regenerative medicineRenal disorders Vascular damage Alzheimer’s disease
Related news items
4,8 million euros for prevention of tuberculosis among people with diabetes in Africa16 July 2019
Reinout van Crevel and Lindsey te Brake have received European funding of 4.8 million euros to lead an international consortium to screen thousands of people with diabetes in Uganda and Tanzania for TB, and investigate the effect and costs of 3 months preventive treatment for TB.read more
Handbook of biomarkers and precision medicine a new publication by Alain van Gool12 July 2019
Alain van Gool published a new handbook on biomarkers and applications in (pre)clinical drug development for precision medicine.read more
Successful Summer School by CMBI, TML and Human Genetics8 July 2019
CMBI, TML and Human Genetics organized a successful Summer School on 'Integrative X-omics Analyses Empowering Personalized Healthcare'.read more
Summer greetings from René Bindels5 July 2019
In this last newsletter before the summer break and before I wish you all a happy holiday, I would like to briefly summarize the first half of 2019 and especially look ahead to the interesting activities that will take place in the second half of the year.read more
Prostate cancer theranostics imaging, surgical guidance, and targeted photodynamic therapy5 July 2019
In Theranostics, Mark Rijpkema and colleagues present the development of a novel multimodal tracer that targets both preoperative imaging, surgical guidance, and targeted photodynamic therapy of PSMA-expressing prostate cancer.read more