A5053073577- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- PI3K/AKT/mTOR signaling in cancer
- Bacteriophages and microbial interactions
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
- Ubiquitin and proteasome pathways
- Mast cells and histamine
- Receptor Mechanisms and Signaling
- Molecular Biology Techniques and Applications
- Viral Infections and Immunology Research
- T-cell and Retrovirus Studies
- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Cytomegalovirus and herpesvirus research
- Enzyme Structure and Function
- Polyamine Metabolism and Applications
- interferon and immune responses
- Microbial Metabolic Engineering and Bioproduction
- Monoclonal and Polyclonal Antibodies Research
- RNA regulation and disease
Max Planck Institute for Biology
2023
Max Planck Institute for Developmental Biology
2011-2021
Max Planck Society
2012-2015
University of California, Berkeley
2012
Columbia University
2009
University of Wisconsin–Madison
2009
Paul Ehrlich Institut
2007
The Netherlands Cancer Institute
2001-2007
Biotechnology Institute
2005
Kyoto University
2005
Abstract The LINE-1 (L1) retrotransposon is an ancient genetic parasite that has written around one-third of the human genome through a ‘copy and paste’ mechanism catalysed by its multifunctional enzyme, open reading frame 2 protein (ORF2p) 1 . ORF2p reverse transcriptase (RT) endonuclease activities have been implicated in pathophysiology cancer 2,3 , autoimmunity 4,5 ageing 6,7 making potential therapeutic target. However, lack structural mechanistic knowledge hampered efforts to...
Alu retrotransposons evolved from 7SL RNA ∼65 million years ago and underwent several rounds of massive expansion in primate genomes. Consequently, the human genome currently harbors 1.1 copies. Some these copies remain actively mobile continue to produce both genetic variation diseases by “jumping” new genomic locations. However, it is unclear how many active exist which subfamilies harbor such Here, we present a comprehensive functional analysis across genome. We cloned variety locations...
The homohexameric (L)Sm protein Hfq is a central mediator of small RNA-based gene regulation in bacteria. recognizes regulatory RNAs (sRNAs) specifically, despite their structural diversity. This specificity could not be explained by previously described RNA-binding modes Hfq. Here we present distinct and preferred mode Hfq–RNA interaction that involves the direct recognition uridine-rich RNA 3′ end. feature common bacterial transcripts as consequence Rho-independent transcription...
The bacterial Sm-like protein Hfq is a central player in the control of gene expression. forms complexes with small regulatory RNAs (sRNAs) that use complementary “seed” sequences to target specific mRNAs. hexameric rings, which preferably bind uridine-rich RNA 3′ ends on their proximal surface and adenine-rich distal surface. However, many reported properties Hfq/sRNA could not be explained by these binding modes. Here, we RybB sRNA identify lateral as third, independent A systematic...
Non-LTR retrotransposons (NLRs) are a unique class of mobile genetic elements that have significant impact on the evolution eukaryotic genomes. However, molecular details and functions their encoded proteins, in particular accessory ORF1p poorly understood. Here, we identify noncanonical RNA-recognition-motifs (RRMs) several phylogenetically unrelated NLR proteins. This provides an explanation for RNA-binding properties clearly shows they not related to retroviral nucleocapsid protein Gag,...
The CCR4–NOT complex plays a crucial role in post-transcriptional mRNA regulation eukaryotic cells. It catalyzes the removal of poly(A) tails, thereby repressing translation and committing mRNAs to decay. conserved core consists catalytic module comprising two deadenylases (CAF1/POP2 CCR4a/b) NOT module, which contains at least NOT1, NOT2 NOT3. NOT1 bridges interaction between modules therefore, acts as scaffold protein for assembly complex. Here, we present crystal structures CAF1-binding...
Argonaute proteins (AGOs) are essential effectors in RNA-mediated gene silencing pathways. They characterized by a bilobal architecture, which one lobe contains the N-terminal and PAZ domains other MID PIWI domains. Here, we present first crystal structure of MID-PIWI from eukaryotic AGO, Neurospora crassa QDE-2 protein. Compared to prokaryotic AGOs, domain orientation is conserved, indicating conserved mode nucleic acid binding. The shows an adaptable surface loop next eukaryote-specific...
The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival a wide range metazoan species. They function by suppressing expression target mRNAs through recruitment effector complexes, which include CCR4–NOT deadenylase complex. Here, we show that three human paralogs (Nanos1–3) interact with CNOT1 C-terminal domain determine structural basis for specific molecular recognition. Nanos1–3 bind short CNOT1-interacting motif (NIM) is conserved all...
Abstract Human ( Hs ) Roquin1 and Roquin2 are RNA-binding proteins that promote mRNA target degradation through the recruitment of CCR4-NOT deadenylase complex implicated in prevention autoimmunity. recruits via a C-terminal region is not conserved or invertebrate Roquin. Here we show Drosophila melanogaster Dm Roquin also interact with their regions. The contains multiple motifs mediate binding. One motif binds to CAF40 subunit complex. crystal structure CAF40-binding (CBM) bound reveals...
Riboswitches reflect a novel concept in gene regulation that is particularly suited for technological adaptation.Therefore, we characterized thermodynamically the ligand binding properties of synthetic, tetracycline (tc)-binding RNA aptamer, which regulates expression dose-dependent manner when inserted into untranslated region an mRNA.In vitro, one molecule tc bound by partially pre-structured and conformationally homogeneous apo-RNA.The dissociation constant 770 pM, as determined...
Argonaute (AGO) proteins are core components of RNA-induced silencing complexes and have essential roles in RNA-mediated gene silencing. They characterized by a bilobal architecture, consisting one lobe containing the amino-terminal PAZ domains another MID PIWI domains. Except for domain, structural information on eukaryotic AGO is not yet available. In this study, we report crystal structure domain protein QDE-2 from Neurospora crassa. This adopts Rossmann-like fold recognizes 5'-terminal...
The nonsense-mediated mRNA decay (NMD) pathway triggers the rapid degradation of aberrant mRNAs containing premature translation termination codons (PTCs). In metazoans, NMD requires three 14-3-3-like proteins: SMG5, SMG6, and SMG7. These proteins are recruited to PTC-containing through interaction their domains with phosphorylated UPF1, central effector. Recruitment SMG7 causes target degradation. this study, we report crystal structure Caenorhabditis elegans SMG5–SMG7 complex....
Mobilization of retrotransposons to new genomic locations is a significant driver mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization mediated primarily by proteins encoded LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early development. Here we show that TEX19.1, induced developmentally programmed DNA hypomethylation, directly interact with the L1-encoded protein L1-ORF1p, stimulate its...
Article11 March 2016Open Access Source DataTransparent process Distinct modes of recruitment the CCR4–NOT complex by Drosophila and vertebrate Nanos Tobias Raisch Department Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany Search more papers this author Dipankar Bhandari Kevin Sabath Sigrun Helms Eugene Valkov Oliver Weichenrieder Corresponding Author Elisa Izaurralde Information Raisch1,‡, Bhandari1,‡, Sabath1, Helms1, Valkov1, 1 1Department ‡These authors...