Structure and function of spliceosomal DEAH-box ATPases
Biol Chem. 2023 Jul 17. doi: 10.1515/hsz-2023-0157. Online ahead of print.ABSTRACTSplicing of precursor mRNAs is a hallmark of eukaryotic cells, performed by a huge macromolecular machine, the spliceosome. Four DEAH-box ATPases are essential components of the spliceosome, which play an important role in the spliceosome activation, the splicing reaction, the release of the spliced mRNA and intron lariat, and the disassembly of the spliceosome. An integrative approach comprising X-ray crystallography, single particle cryo electron microscopy, single molecule FRET, and molecular dynamics simulations provided deep insights int...
Source: Biological Chemistry - July 13, 2023 Category: Chemistry Authors: Marieke Enders Piotr Neumann Achim Dickmanns Ralf Ficner Source Type: research

The DEAD-box RNA helicase Dbp5 is a key protein that couples multiple steps in gene expression
Biol Chem. 2023 Jul 13. doi: 10.1515/hsz-2023-0130. Online ahead of print.ABSTRACTCell viability largely depends on the surveillance of mRNA export and translation. Upon pre-mRNA processing and nuclear quality control, mature mRNAs are exported into the cytoplasm via Mex67-Mtr2 attachment. At the cytoplasmic site of the nuclear pore complex, the export receptor is displaced by the action of the DEAD-box RNA helicase Dbp5. Subsequent quality control of the open reading frame requires translation. Our studies suggest an involvement of Dbp5 in cytoplasmic no-go-and non-stop decay. Most importantly, we have also identified a k...
Source: Biological Chemistry - July 12, 2023 Category: Chemistry Authors: Luisa Querl Heike Krebber Source Type: research

The human long non-coding RNA LINC00941 and its modes of action in health and disease
Biol Chem. 2023 Jul 10. doi: 10.1515/hsz-2023-0183. Online ahead of print.ABSTRACTLong non-coding RNAs have gained attention in recent years as they were shown to play crucial roles in the regulation of cellular processes, but the understanding of the exact mechanisms is still incomplete in most cases. This is also true for long non-coding RNA LINC00941, which was recently found to be highly upregulated in various types of cancer influencing cell proliferation and metastasis. Initial studies could not elucidate the mode of action to understand the role and real impact of LINC00941 in tissue homeostasis and cancer developme...
Source: Biological Chemistry - July 7, 2023 Category: Chemistry Authors: Eva Morgenstern Markus Kretz Source Type: research

Translation termination in human mitochondria  - substrate specificity of mitochondrial release factors
We describe how mtRF1a resembles bacterial RF1 mechanistically and summarize in vitro and recent in vivo data leading to the conclusion of mtRF1a being the major mitochondrial release factor. On the other hand, we discuss the ongoing debate about the function of the second codon-dependent mitochondrial release factor mtRF1 regarding its role as a specialized termination factor. Finally, we link defects in mitochondrial translation termination to the activation of mitochondrial rescue mechanisms highlighting the importance of ribosome-associated quality control for sufficient respiratory function and therefore for human hea...
Source: Biological Chemistry - June 28, 2023 Category: Chemistry Authors: Franziska Nadler Ricarda Richter-Dennerlein Source Type: research