Claudia Höbartner, Katherine E. Bohnsack, Markus T. Bohnsack
{"title":"How Natural Enzymes and Synthetic Ribozymes Generate Methylated Nucleotides in RNA","authors":"Claudia Höbartner, Katherine E. Bohnsack, Markus T. Bohnsack","doi":"10.1146/annurev-biochem-030222-112310","DOIUrl":"https://doi.org/10.1146/annurev-biochem-030222-112310","url":null,"abstract":"Methylation of RNA nucleotides represents an important layer of gene expression regulation, and perturbation of the RNA methylome is associated with pathophysiology. In cells, RNA methylations are installed by RNA methyltransferases (RNMTs) that are specialized to catalyze particular types of methylation (ribose or different base positions). Furthermore, RNMTs must specifically recognize their appropriate target RNAs within the RNA-dense cellular environment. Some RNMTs are catalytically active alone and achieve target specificity via recognition of sequence motifs and/or RNA structures. Others function together with protein cofactors that can influence stability, <jats:italic>S</jats:italic>-adenosyl-L-methionine binding, and RNA affinity as well as aiding specific recruitment and catalytic activity. Association of RNMTs with guide RNAs represents an alternative mechanism to direct site-specific methylation by an RNMT that lacks intrinsic specificity. Recently, ribozyme-catalyzed methylation of RNA has been achieved in vitro, and here, we compare these different strategies for RNA methylation from structural and mechanistic perspectives.","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural and Engineered Guide RNA–directed Transposition with CRISPR-Associated Tn7-like Transposons","authors":"Shan-Chi Hsieh, Joseph E. Peters","doi":"10.1146/annurev-biochem-030122-041908","DOIUrl":"https://doi.org/10.1146/annurev-biochem-030122-041908","url":null,"abstract":"CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated nuclease) defense systems have been naturally coopted for guide RNA–directed transposition on multiple occasions. In all cases, cooption occurred with diverse elements related to the bacterial transposon Tn7. Tn7 tightly controls transposition; the transposase is activated only when special targets are recognized by dedicated target-site selection proteins. Tn7 and the Tn7-like elements that coopted CRISPR–Cas systems evolved complementary targeting pathways: one that recognizes a highly conserved site in the chromosome and a second pathway that targets mobile plasmids capable of cell-to-cell transfer. Tn7 and Tn7-like elements deliver a single integration into the site they recognize and also control the orientation of the integration event, providing future potential for use as programmable gene-integration tools. Early work has shown that guide RNA–directed transposition systems can be adapted to diverse hosts, even within microbial communities, suggesting great potential for engineering these systems as powerful gene-editing tools.","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"59 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Story of RNA Unfolded: The Molecular Function of DEAD- and DExH-Box ATPases and Their Complex Relationship with Membraneless Organelles","authors":"Kerstin Dörner, Maria Hondele","doi":"10.1146/annurev-biochem-052521-121259","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052521-121259","url":null,"abstract":"DEAD- and DExH-box ATPases (DDX/DHXs) are abundant and highly conserved cellular enzymes ubiquitously involved in RNA processing. By remodeling RNA–RNA and RNA–protein interactions, they often function as gatekeepers that control the progression of diverse RNA maturation steps. Intriguingly, most DDX/DHXs localize to membraneless organelles (MLOs) such as nucleoli, nuclear speckles, stress granules, or processing bodies. Recent findings suggest not only that localization to MLOs can promote interaction between DDX/DHXs and their targets but also that DDX/DHXs are key regulators of MLO formation and turnover through their condensation and ATPase activity. In this review, we describe the molecular function of DDX/DHXs in ribosome biogenesis, messenger RNA splicing, export, translation, and storage or decay as well as their association with prominent MLOs. We discuss how the enzymatic function of DDX/DHXs in RNA processing is linked to DDX/DHX condensation, the accumulation of ribonucleoprotein particles and MLO dynamics. Future research will reveal how these processes orchestrate the RNA life cycle in MLO space and DDX/DHX time.","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"8 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Endo-Lysosomal Damage Response","authors":"Hemmo Meyer, Bojana Kravic","doi":"10.1146/annurev-biochem-030222-102505","DOIUrl":"https://doi.org/10.1146/annurev-biochem-030222-102505","url":null,"abstract":"Lysosomes are the degradative endpoints of material delivered by endocytosis and autophagy and are therefore particularly prone to damage. Membrane permeabilization or full rupture of lysosomal or late endosomal compartments is highly deleterious because it threatens cellular homeostasis and can elicit cell death and inflammatory signaling. Cells have developed a complex response to endo-lysosomal damage that largely consists of three branches. Initially, a number of repair pathways are activated to restore the integrity of the lysosomal membrane. If repair fails or if damage is too extensive, lysosomes are isolated and degraded by a form of selective autophagy termed lysophagy. Meanwhile, an mTORC1-governed signaling cascade drives biogenesis and regeneration of new lysosomal components to reestablish the full lysosomal capacity of the cell. This damage response is vital to counteract the effects of various conditions, including neurodegeneration and infection, and can constitute a critical vulnerability in cancer cells.","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"97 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural Biochemistry of Muscle Contraction.","authors":"Zhexin Wang, Stefan Raunser","doi":"10.1146/annurev-biochem-052521-042909","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052521-042909","url":null,"abstract":"<p><p>Muscles are essential for movement and heart function. Contraction and relaxation of muscles rely on the sliding of two types of filaments-the thin filament and the thick myosin filament. The thin filament is composed mainly of filamentous actin (F-actin), tropomyosin, and troponin. Additionally, several other proteins are involved in the contraction mechanism, and their malfunction can lead to diverse muscle diseases, such as cardiomyopathies. We review recent high-resolution structural data that explain the mechanism of action of muscle proteins at an unprecedented level of molecular detail. We focus on the molecular structures of the components of the thin and thick filaments and highlight the mechanisms underlying force generation through actin-myosin interactions, as well as Ca<sup>2+</sup>-dependent regulation via the dihydropyridine receptor, the ryanodine receptor, and troponin. We particularly emphasize the impact of cryo-electron microscopy and cryo-electron tomography in leading muscle research into a new era.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"411-433"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9662512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolás Nieto Moreno, Anouk M Olthof, Jesper Q Svejstrup
{"title":"Transcription-Coupled Nucleotide Excision Repair and the Transcriptional Response to UV-Induced DNA Damage.","authors":"Nicolás Nieto Moreno, Anouk M Olthof, Jesper Q Svejstrup","doi":"10.1146/annurev-biochem-052621-091205","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052621-091205","url":null,"abstract":"<p><p>Ultraviolet (UV) irradiation and other genotoxic stresses induce bulky DNA lesions, which threaten genome stability and cell viability. Cells have evolved two main repair pathways to remove such lesions: global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The modes by which these subpathways recognize DNA lesions are distinct, but they converge onto the same downstream steps for DNA repair. Here, we first summarize the current understanding of these repair mechanisms, specifically focusing on the roles of stalled RNA polymerase II, Cockayne syndrome protein B (CSB), CSA and UV-stimulated scaffold protein A (UVSSA) in TC-NER. We also discuss the intriguing role of protein ubiquitylation in this process. Additionally, we highlight key aspects of the effect of UV irradiation on transcription and describe the role of signaling cascades in orchestrating this response. Finally, we describe the pathogenic mechanisms underlying xeroderma pigmentosum and Cockayne syndrome, the two main diseases linked to mutations in NER factors.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"81-113"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9671476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher P Selby, Laura A Lindsey-Boltz, Wentao Li, Aziz Sancar
{"title":"Molecular Mechanisms of Transcription-Coupled Repair.","authors":"Christopher P Selby, Laura A Lindsey-Boltz, Wentao Li, Aziz Sancar","doi":"10.1146/annurev-biochem-041522-034232","DOIUrl":"https://doi.org/10.1146/annurev-biochem-041522-034232","url":null,"abstract":"<p><p>Transcription-coupled repair (TCR), discovered as preferential nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers located in transcribed mammalian genes compared to those in nontranscribed regions of the genome, is defined as faster repair of the transcribed strand versus the nontranscribed strand in transcribed genes. The phenomenon, universal in model organisms including <i>Escherichia coli</i>, yeast, <i>Arabidopsis</i>, mice, and humans, involves a translocase that interacts with both RNA polymerase stalled at damage in the transcribed strand and nucleotide excision repair proteins to accelerate repair. <i>Drosophila</i>, a notable exception, exhibits TCR but lacks an obvious TCR translocase. Mutations inactivating TCR genes cause increased damage-induced mutagenesis in <i>E. coli</i> and severe neurological and UV sensitivity syndromes in humans. To date, only <i>E. coli</i> TCR has been reconstituted in vitro with purified proteins. Detailed investigations of TCR using genome-wide next-generation sequencing methods, cryo-electron microscopy, single-molecule analysis, and other approaches have revealed fascinating mechanisms.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"115-144"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9662513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"3'-End Processing of Eukaryotic mRNA: Machinery, Regulation, and Impact on Gene Expression.","authors":"Vytautė Boreikaitė, Lori A Passmore","doi":"10.1146/annurev-biochem-052521-012445","DOIUrl":"10.1146/annurev-biochem-052521-012445","url":null,"abstract":"<p><p>Formation of the 3' end of a eukaryotic mRNA is a key step in the production of a mature transcript. This process is mediated by a number of protein factors that cleave the pre-mRNA, add a poly(A) tail, and regulate transcription by protein dephosphorylation. Cleavage and polyadenylation specificity factor (CPSF) in humans, or cleavage and polyadenylation factor (CPF) in yeast, coordinates these enzymatic activities with each other, with RNA recognition, and with transcription. The site of pre-mRNA cleavage can strongly influence the translation, stability, and localization of the mRNA. Hence, cleavage site selection is highly regulated. The length of the poly(A) tail is also controlled to ensure that every transcript has a similar tail when it is exported from the nucleus. In this review, we summarize new mechanistic insights into mRNA 3'-end processing obtained through structural studies and biochemical reconstitution and outline outstanding questions in the field.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"199-225"},"PeriodicalIF":12.1,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10002692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rajesh K Harijan, Subhadra Dalwani, Tiila-Riikka Kiema, Rajaram Venkatesan, Rik K Wierenga
{"title":"Thiolase: A Versatile Biocatalyst Employing Coenzyme A-Thioester Chemistry for Making and Breaking C-C Bonds.","authors":"Rajesh K Harijan, Subhadra Dalwani, Tiila-Riikka Kiema, Rajaram Venkatesan, Rik K Wierenga","doi":"10.1146/annurev-biochem-052521-033746","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052521-033746","url":null,"abstract":"<p><p>Thiolases are CoA-dependent enzymes that catalyze the thiolytic cleavage of 3-ketoacyl-CoA, as well as its reverse reaction, which is the thioester-dependent Claisen condensation reaction. Thiolases are dimers or tetramers (dimers of dimers). All thiolases have two reactive cysteines: (<i>a</i>) a nucleophilic cysteine, which forms a covalent intermediate, and (<i>b</i>) an acid/base cysteine. The best characterized thiolase is the <i>Zoogloea ramigera</i> thiolase, which is a bacterial biosynthetic thiolase belonging to the CT-thiolase subfamily. The thiolase active site is also characterized by two oxyanion holes, two active site waters, and four catalytic loops with characteristic amino acid sequence fingerprints. Three thiolase subfamilies can be identified, each characterized by a unique sequence fingerprint for one of their catalytic loops, which causes unique active site properties. Recent insights concerning the thiolase reaction mechanism, as obtained from recent structural studies, as well as from classical and recent enzymological studies, are addressed, and open questions are discussed.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"351-384"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian M Hoffman, William E Broderick, Joan B Broderick
{"title":"Mechanism of Radical Initiation in the Radical SAM Enzyme Superfamily.","authors":"Brian M Hoffman, William E Broderick, Joan B Broderick","doi":"10.1146/annurev-biochem-052621-090638","DOIUrl":"10.1146/annurev-biochem-052621-090638","url":null,"abstract":"<p><p>Radical <i>S</i>-adenosylmethionine (SAM) enzymes use a site-differentiated [4Fe-4S] cluster and SAM to initiate radical reactions through liberation of the 5'-deoxyadenosyl (5'-dAdo•) radical. They form the largest enzyme superfamily, with more than 700,000 unique sequences currently, and their numbers continue to grow as a result of ongoing bioinformatics efforts. The range of extremely diverse, highly regio- and stereo-specific reactions known to be catalyzed by radical SAM superfamily members is remarkable. The common mechanism of radical initiation in the radical SAM superfamily is the focus of this review. Most surprising is the presence of an organometallic intermediate, Ω, exhibiting an Fe-C5'-adenosyl bond. Regioselective reductive cleavage of the SAM S-C5' bond produces 5'-dAdo• to form Ω, with the regioselectivity originating in the Jahn-Teller effect. Ω liberates the free 5'-dAdo• as the catalytically active intermediate through homolysis of the Fe-C5' bond, in analogy to Co-C5' bond homolysis in B<sub>12</sub>, which was once viewed as biology's choice of radical generator.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"333-349"},"PeriodicalIF":12.1,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9662524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}