A5041558179- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- Molecular Biology Techniques and Applications
- Nuclear Structure and Function
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer therapeutics and mechanisms
- Bacterial Genetics and Biotechnology
- Fungal and yeast genetics research
- Neurogenetic and Muscular Disorders Research
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- biodegradable polymer synthesis and properties
- Lipid metabolism and biosynthesis
- RNA regulation and disease
- Muscle Physiology and Disorders
- Heat shock proteins research
- Chemical Synthesis and Analysis
- Plant Genetic and Mutation Studies
- Mitochondrial Function and Pathology
- Skin and Cellular Biology Research
Martin Luther University Halle-Wittenberg
2014-2023
Max Planck Innovation
2009
Max Planck Society
2009
Medizinische Hochschule Hannover
2002
Justus-Liebig-Universität Gießen
1996-2000
University Hospital in Halle
2000
University of Basel
1990-1999
University of Wisconsin–Madison
1992-1994
European Molecular Biology Laboratory
1994
University of Lausanne
1994
The RNA-binding protein IGF2BP1 (IGF-II mRNA binding 1) stabilizes the c-myc RNA by associating with Coding Region instability Determinant (CRD). If and how other proteins cooperate in promoting stabilization of via CRD remained elusive. Here, we identify various that associate an RNA-dependent fashion. Four these (HNRNPU, SYNCRIP, YBX1, DHX9) were essential to ensure CRD. These factors a CRD-dependent manner, co-distribute non-polysomal fractions comprising mRNA, colocalize cytoplasm. A...
Cleavage and polyadenylation specificity factor (CPSF) is the central component of 3′ processing machinery for polyadenylated mRNAs in metazoans: CPSF recognizes signal AAUAAA, providing sequence both pre-mRNA cleavage polyadenylation, catalyzes cleavage. Here we show that seven polypeptides have been proposed to constitute CPSF, only four (CPSF160, CPSF30, hFip1, WDR33) are necessary sufficient reconstitute a subcomplex active AAUAAA-dependent whereas CPSF100, CPSF73, symplekin dispensable....
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of the caused short (GCG)8–13 expansions in PABP2 gene. This gene encodes poly(A) binding protein 2 (PABP2), abundant nuclear that binds with high affinity to nascent tails, stimulating their extension controlling length. In this work we report detected filamentous inclusions, which are pathological...
3′-Exonucleolytic removal of the poly(A) tail is first and often rate-limiting step in decay many eucaryotic mRNAs. In a cytoplasmic extract from HeLa cells, mRNA was degraded 3′-end. agreement with earlierin vivo observations, prominent intermediates differed length by about 30 nucleotides. The Mg2+-dependent, poly(A)-specific 3′-exoribonuclease responsible for this shortening activity purified calf thymus. A polypeptide 74 kDa copurified activity. deadenylating nuclease (DAN) required free...
Poly(A) tails of mRNAs are synthesized in the cell nucleus with a defined length, approximately 250 nucleotides mammalian cells. The same type length control is seen an vitro polyadenylation system reconstituted from three proteins: poly(A) polymerase, cleavage and specificity factor (CPSF), nuclear poly(A)-binding protein (PABPN1). CPSF, binding signal AAUAAA, PABPN1, growing tail, cooperatively stimulate polymerase such that complete tail one processive event, which terminates at...
Polyadenylation of messenger RNA precursors requires the nucleotide sequence AAUAAA and two factors: poly(A) polymerase a specificity factor termed cleavage polyadenylation (CPF). We have purified CPF from calf thymus HeLa cells to near homogeneity. Four polypeptides with molecular masses 160, 100, 73, 30 kDa cofractionate activity. Glycerol gradient centrifugation gel filtration indicate that these four proteins form one large complex sedimentation constant 12 S, Stokes radius 100 A, native...
The CCR4-NOT complex is the main enzyme catalyzing deadenylation of mRNA. We have investigated composition this in Drosophila melanogaster by immunoprecipitation with a monoclonal antibody directed against NOT1. CCR4, CAF1 (=POP2), NOT1, NOT2, NOT3, and CAF40 subunits were associated stable complex, but NOT4 was not. Factors known to be involved mRNA regulation prominent among other proteins coprecipitated as analyzed mass spectrometry. localized mostly cytoplasm did not appear major...
Small nucleolar and small Cajal body RNAs (snoRNAs scaRNAs) of the H/ACA box C/D type are generated by exonucleolytic shortening longer precursors. Removal last few nucleotides at 3′ end is known to be a distinct step. We report that, in human cells, knock-down poly(A) specific ribonuclease (PARN), previously implicated only mRNA metabolism, causes accumulation oligoadenylated processing intermediates but not RNAs. In agreement with role PARN snoRNA scaRNA processing, enzyme concentrated...
The 3' ends of almost all eukaryotic mRNAs are generated in an essential two-step processing reaction: endonucleolytic cleavage extended precursor followed by the addition a poly(A) tail. By reconstituting reaction from overproduced and purified proteins, we provide minimal list 14 polypeptides that two stimulatory for RNA processing. In depending on polyadenylation signal AAUAAA, reconstituted system cleaves pre-mRNA at single preferred site corresponding to one used vivo. Among factor I...
Arginine methylation is a post-translational modification found mostly in RNA-binding proteins. Poly(A)-binding protein II from calf thymus was shown by mass spectrometry and sequencing to contain<i>N</i> <sup>G</sup>,<i>N</i> <sup>G</sup>-dimethylarginine at 13 positions its amino acid sequence. Two additional arginine residues were partially methylated. Almost all of the modified Arg-Xaa-Arg clusters C terminus protein. These motifs are distinct Arg-Gly-Gly that have been previously...