Brr2p RNA helicase with a split personality: insights into structure and function

2010 ◽  
Vol 38 (4) ◽  
pp. 1105-1109 ◽  
Author(s):  
Daniela Hahn ◽  
Jean D. Beggs
Keyword(s):  
Domain Architecture ◽  
Rna Helicase ◽  
Structure And Function ◽  
Mrna Splicing ◽  
Eye Disease ◽  
Rna Helicases ◽  
Cellular Processes ◽  
Biochemical Studies ◽  
Split Personality ◽  
And Function

RNA helicases are involved in many cellular processes. Pre-mRNA splicing requires eight different DExD/H-box RNA helicases, which facilitate spliceosome assembly and remodelling of the intricate network of RNA rearrangements that are central to the splicing process. Brr2p, one of the spliceosomal RNA helicases, stands out through its unusual domain architecture. In the present review we highlight the advances made by recent structural and biochemical studies that have important implications for the mechanism and regulation of Brr2p activity. We also discuss the involvement of human Brr2 in retinitis pigmentosa, a degenerative eye disease, and how its functions in splicing might connect to the molecular pathology of the disease.

scholarly journals Structural and functional analysis of the RNA helicase Prp43 from the thermophilic eukaryoteChaetomium thermophilum

2016 ◽  
Vol 72 (2) ◽  
pp. 112-120 ◽  
Author(s):  
Marcel J. Tauchert ◽  
Jean-Baptiste Fourmann ◽  
Henning Christian ◽  
Reinhard Lührmann ◽  
Ralf Ficner
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Functional Analysis ◽  
Rna Helicase ◽  
Mrna Splicing ◽  
Rna Helicases ◽  
Cellular Processes ◽  
Chaetomium Thermophilum ◽  
Rrna Maturation

RNA helicases are indispensable for all organisms in each domain of life and have implications in numerous cellular processes. The DEAH-box RNA helicase Prp43 is involved in pre-mRNA splicing as well as rRNA maturation. Here, the crystal structure ofChaetomium thermophilumPrp43 at 2.9 Å resolution is revealed. Furthermore, it is demonstrated that Prp43 fromC. thermophilumis capable of functionally replacing its orthologue fromSaccharomyces cerevisiaein spliceosomal disassembly assays.

scholarly journals The structure and function of centriolar rootlets

2021 ◽  
Vol 134 (16) ◽  
Author(s):  
Robert Mahen
Keyword(s):  
Cellular Function ◽  
Structure And Function ◽  
Cellular Systems ◽  
Macromolecular Assemblies ◽  
Cellular Processes ◽  
Holistic Understanding ◽  
Eukaryotic Organisms ◽  
And Function ◽  
Knockout Animals

ABSTRACT To gain a holistic understanding of cellular function, we must understand not just the role of individual organelles, but also how multiple macromolecular assemblies function collectively. Centrioles produce fundamental cellular processes through their ability to organise cytoskeletal fibres. In addition to nucleating microtubules, centrioles form lesser-known polymers, termed rootlets. Rootlets were identified over a 100 years ago and have been documented morphologically since by electron microscopy in different eukaryotic organisms. Rootlet-knockout animals have been created in various systems, providing insight into their physiological functions. However, the precise structure and function of rootlets is still enigmatic. Here, I consider common themes of rootlet function and assembly across diverse cellular systems. I suggest that the capability of rootlets to form physical links from centrioles to other cellular structures is a general principle unifying their functions in diverse cells and serves as an example of how cellular function arises from collective organellar activity.

scholarly journals Viperin catalyzes methionine oxidation to promote protein expression and function of helicases

2019 ◽  
Vol 5 (8) ◽  
pp. eaax1031 ◽  
Author(s):  
Lei Bai ◽  
Jiazhen Dong ◽  
Zhenqiu Liu ◽  
Youliang Rao ◽  
Pinghui Feng ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Methionine Oxidation ◽  
Biological Processes ◽  
Loss Of Function ◽  
Rna Helicases ◽  
Dna And Rna ◽  
Biochemical Studies ◽  
The Stability ◽  
And Function

Helicases play pivotal roles in fundamental biological processes, and posttranslational modifications regulate the localization, function, and stability of helicases. Here, we report that methionine oxidation of representative helicases, including DNA and RNA helicases of viral (ORF44 of KSHV) and cellular (MCM7 and RIG-I) origin, promotes their expression and functions. Cellular viperin, a major antiviral interferon-stimulated gene whose functions beyond host defense remain largely unknown, catalyzes the methionine oxidation of these helicases. Moreover, biochemical studies entailing loss-of-function mutations of helicases and a pharmacological inhibitor interfering with lipid metabolism and, hence, decreasing viperin activity indicate that methionine oxidation potently increases the stability and enzyme activity of these helicases that are critical for DNA replication and immune activation. Our work uncovers a pivotal role of viperin in catalyzing the methionine oxidation of helicases that are implicated in diverse fundamental biological processes.

scholarly journals Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism

2018 ◽  
Vol 19 (12) ◽  
pp. 3839 ◽  
Author(s):  
Daniel Peters ◽  
Laura Kay ◽  
Jeyanthy Eswaran ◽  
Jeremy Lakey ◽  
Meera Soundararajan
Keyword(s):  
Catalytic Mechanism ◽  
Catalytic Domain ◽  
Domain Architecture ◽  
Subcellular Localisation ◽  
Cellular Processes ◽  
Calcium Sensing ◽  
And Function ◽  
Arginine Finger ◽  
Catalytic Functions ◽  
Unique Domain

Mitochondria are highly dynamic organelles that play a central role in multiple cellular processes, including energy metabolism, calcium homeostasis and apoptosis. Miro proteins (Miros) are “atypical” Ras superfamily GTPases that display unique domain architecture and subcellular localisation regulating mitochondrial transport, autophagy and calcium sensing. Here, we present systematic catalytic domain characterisation and structural analyses of human Miros. Despite lacking key conserved catalytic residues (equivalent to Ras Y32, T35, G60 and Q61), the Miro N-terminal GTPase domains display GTPase activity. Surprisingly, the C-terminal GTPase domains previously assumed to be “relic” domains were also active. Moreover, Miros show substrate promiscuity and function as NTPases. Molecular docking and structural analyses of Miros revealed unusual features in the Switch I and II regions, facilitating promiscuous substrate binding and suggesting the usage of a novel hydrolytic mechanism. The key substitution in position 13 in the Miros leads us to suggest the existence of an “internal arginine finger”, allowing an unusual catalytic mechanism that does not require GAP protein. Together, the data presented here indicate novel catalytic functions of human Miro atypical GTPases through altered catalytic mechanisms.

Structural modelling studies and immunoprophylactic potential ofBrugia malayiDEAD Box RNA helicase

Parasitology ◽  
2013 ◽  
Vol 140 (8) ◽  
pp. 1016-1025 ◽  
Author(s):  
MEGHNA SINGH ◽  
NIDHI SHRIVASTAVA ◽  
UZMA SAQIB ◽  
MOHAMMAD IMRAN SIDDIQI ◽  
SHAILJA MISRA-BHATTACHARYA
Keyword(s):  
Adverse Outcome ◽  
3D Structure ◽  
Rna Helicase ◽  
Mrna Splicing ◽  
Oxygen Species ◽  
Rna Helicases ◽  
Infective Larvae ◽  
Dead Box ◽  
Modelling Studies ◽  
Mastomys Coucha

SUMMARYDEAD Box RNA helicases are essential enzymes that are involved in RNA metabolic processes such as transcription, pre-mRNA splicing, translation initiation and RNA decay. We have previously over-expressed and biochemically characterized an immunodominant cDNA clone encoding DEAD box RNA helicase (BmL3-Helicase) isolated by immunoscreening of the larval stage cDNA library ofBrugia malayi.In the current study, the 3D structure was determined and the immunoprophylactic efficacy of BmL3-Helicase was investigated by immunizingMastomys couchawith the recombinant protein and subsequently challenging withB. malayiinfective larvae. The immunization had an adverse outcome on the establishment of challenged larvae resulting in a 67·4% reduction in adult parasite recovery, a 86·7% decrease in the microfilarial density and profound sterility of the recovered female worms. The immune response thus generated was investigated by measuring the levels of specific antibodies including IgG subclasses, reactive oxygen species and cytokines.

scholarly journals RNA interactomics: recent advances and remaining challenges

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1824 ◽  
Author(s):  
Brigitte Schönberger ◽  
Christoph Schaal ◽  
Richard Schäfer ◽  
Björn Voß
Keyword(s):  
High Throughput ◽  
Rna Structure ◽  
Living Cells ◽  
Structure And Function ◽  
Cellular Processes ◽  
Recent Advances ◽  
Regulatory Systems ◽  
Rna Duplexes ◽  
And Function

Tight regulation of cellular processes is key to the development of complex organisms but also vital for simpler ones. During evolution, different regulatory systems have emerged, among them RNA-based regulation that is carried out mainly by intramolecular and intermolecular RNA–RNA interactions. However, methods for the transcriptome-wide detection of these interactions were long unavailable. Recently, three publications described high-throughput methods to directly detect RNA duplexes in living cells. This promises to enable in-depth studies of RNA-based regulation and will narrow the gaps in our understanding of RNA structure and function. In this review, we highlight the benefits of these methods and their commonalities and differences and, in particular, point to methodological shortcomings that hamper their wider application. We conclude by presenting ideas for how to overcome these problems and commenting on the prospects we see in this area of research.

scholarly journals Characterizing the Structure and Function of the N-Terminus of Schizosaccharomyces Pombe Cdc5, a Pre-Mrna Splicing Factor

2014 ◽  
Vol 106 (2) ◽  
pp. 429a
Author(s):  
Scott E. Collier ◽  
Dungeng Peng ◽  
Markus Voehler ◽  
Nicholas Reiter ◽  
Melanie Ohi
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Structure And Function ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
N Terminus ◽  
And Function

Computational identification of protein S-sulfenylation sites by incorporating the multiple sequence features information

2017 ◽  
Vol 13 (12) ◽  
pp. 2545-2550 ◽  
Author(s):  
Md. Mehedi Hasan ◽  
Dianjing Guo ◽  
Hiroyuki Kurata
Keyword(s):  
Protein Structure ◽  
Posttranslational Modification ◽  
Protein S ◽  
Structure And Function ◽  
Major Type ◽  
Multiple Sequence ◽  
Sequence Features ◽  
Cellular Processes ◽  
Computational Identification ◽  
And Function

Cysteine S-sulfenylation is a major type of posttranslational modification that contributes to protein structure and function regulation in many cellular processes.

The haloarchaeal chromosome replication machinery

2009 ◽  
Vol 37 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Stuart A. MacNeill
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Biochemical Analysis ◽  
Structure And Function ◽  
Haloferax Volcanii ◽  
Eukaryotic Cells ◽  
Replication Machinery ◽  
Chromosomal Dna ◽  
Biochemical Studies ◽  
And Function

The powerful combination of genetic and biochemical analysis has provided many key insights into the structure and function of the chromosomal DNA replication machineries of bacterial and eukaryotic cells. In contrast, in the archaea, biochemical studies have dominated, mainly due to the absence of efficient genetic systems for these organisms. This situation is changing, however, and, in this regard, the genetically tractable haloarchaea Haloferax volcanii and Halobacterium sp. NRC-1 are emerging as key models. In the present review, I give an overview of the components of the replication machinery in the haloarchaea, with particular emphasis on the protein factors presumed to travel with the replication fork.

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