{"title":"The molecular structure of long non-coding RNAs: emerging patterns and functional implications.","authors":"Isabel Chillón, Marco Marcia","doi":"10.1080/10409238.2020.1828259","DOIUrl":"https://doi.org/10.1080/10409238.2020.1828259","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are recently-discovered transcripts that regulate vital cellular processes and are crucially connected to diseases. Despite their unprecedented molecular complexity, it is emerging that lncRNAs possess distinct structural motifs. Remarkably, the 3D shape and topology of full-length, native lncRNAs have been visualized for the first time in the last year. These studies reveal that lncRNA structures dictate lncRNA functions. Here, we review experimentally determined lncRNA structures and emphasize that lncRNA structural characterization requires synergistic integration of computational, biochemical and biophysical approaches. Based on these emerging paradigms, we discuss how to overcome the challenges posed by the complex molecular architecture of lncRNAs, with the goal of obtaining a detailed understanding of lncRNA functions and molecular mechanisms in the future.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 6","pages":"662-690"},"PeriodicalIF":6.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2020.1828259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38574197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From canonical to modified nucleotides: balancing translation and metabolism.","authors":"Federica Accornero, Robert L Ross, Juan D Alfonzo","doi":"10.1080/10409238.2020.1818685","DOIUrl":"https://doi.org/10.1080/10409238.2020.1818685","url":null,"abstract":"Abstract Every type of nucleic acid in cells may undergo some kind of post-replicative or post-transcriptional chemical modification. Recent evidence has highlighted their importance in biology and their chemical complexity. In the following pages, we will describe new discoveries of modifications, with a focus on tRNA and mRNA. We will highlight current challenges and advances in modification detection and we will discuss how changes in nucleotide post-transcriptional modifications may affect cell homeostasis leading to malfunction. Although, RNA modifications prevail in all forms of life, the present review will focus on eukaryotic systems, where the great degree of intracellular compartmentalization provides barriers and filters for the level at which a given RNA is modified and will of course affect its fate and function. Additionally, although we will mention rRNA modification and modifications of the mRNA 5’-CAP structure, this will only be discussed in passing, as many substantive reviews have been written on these subjects. Here we will not spend much time describing all the possible modifications that have been observed; truly a daunting task. For reference, Bujnicki and coworkers have created MODOMICS, a useful repository for all types of modifications and their associated enzymes. Instead we will discuss a few examples, which illustrate our arguments on the connection of modifications, metabolism and ultimately translation. The fact remains, a full understanding of the long reach of nucleic acid modifications in cells requires both a global and targeted study of unprecedented scale, which at the moment may well be limited only by technology.","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 6","pages":"525-540"},"PeriodicalIF":6.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2020.1818685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38383196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An updated perspective on the polymerase division of labor during eukaryotic DNA replication.","authors":"Thomas A Guilliam, Joseph T P Yeeles","doi":"10.1080/10409238.2020.1811630","DOIUrl":"https://doi.org/10.1080/10409238.2020.1811630","url":null,"abstract":"<p><p>In eukaryotes three DNA polymerases (Pols), α, δ, and ε, are tasked with bulk DNA synthesis of nascent strands during genome duplication. Most evidence supports a model where Pol α initiates DNA synthesis before Pol ε and Pol δ replicate the leading and lagging strands, respectively. However, a number of recent reports, enabled by advances in biochemical and genetic techniques, have highlighted emerging roles for Pol δ in all stages of leading-strand synthesis; initiation, elongation, and termination, as well as fork restart. By focusing on these studies, this review provides an updated perspective on the division of labor between the replicative polymerases during DNA replication.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 5","pages":"469-481"},"PeriodicalIF":6.5,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2020.1811630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38439204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Gorka, Dmitry A Cherepanov, Alexey Yu Semenov, John H Golbeck
{"title":"Control of electron transfer by protein dynamics in photosynthetic reaction centers.","authors":"Michael Gorka, Dmitry A Cherepanov, Alexey Yu Semenov, John H Golbeck","doi":"10.1080/10409238.2020.1810623","DOIUrl":"https://doi.org/10.1080/10409238.2020.1810623","url":null,"abstract":"<p><p>Trehalose and glycerol are low molecular mass sugars/polyols that have found widespread use in the protection of native protein states, in both short- and long-term storage of biological materials, and as a means of understanding protein dynamics. These myriad uses are often attributed to their ability to form an amorphous glassy matrix. In glycerol, the glass is formed only at cryogenic temperatures, while in trehalose, the glass is formed at room temperature, but only upon dehydration of the sample. While much work has been carried out to elucidate a mechanistic view of how each of these matrices interact with proteins to provide stability, rarely have the effects of these two independent systems been directly compared to each other. This review aims to compile decades of research on how different glassy matrices affect two types of photosynthetic proteins: (i) the Type II bacterial reaction center from <i>Rhodobacter sphaeroides</i> and (ii) the Type I Photosystem I reaction center from cyanobacteria. By comparing aggregate data on electron transfer, protein structure, and protein dynamics, it appears that the effects of these two distinct matrices are remarkably similar. Both seem to cause a \"tightening\" of the solvation shell when in a glassy state, resulting in severely restricted conformational mobility of the protein and associated water molecules. Thus, trehalose appears to be able to mimic, at room temperature, nearly all of the effects on protein dynamics observed in low temperature glycerol glasses.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 5","pages":"425-468"},"PeriodicalIF":6.5,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2020.1810623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38343482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair.","authors":"Colleen C Caldwell, Maria Spies","doi":"10.1080/10409238.2020.1813070","DOIUrl":"10.1080/10409238.2020.1813070","url":null,"abstract":"<p><p>The heterotrimeric eukaryotic Replication protein A (RPA) is a master regulator of numerous DNA metabolic processes. For a long time, it has been viewed as an inert protector of ssDNA and a platform for assembly of various genome maintenance and signaling machines. Later, the modular organization of the RPA DNA binding domains suggested a possibility for dynamic interaction with ssDNA. This modular organization has inspired several models for the RPA-ssDNA interaction that aimed to explain how RPA, the high-affinity ssDNA binding protein, is replaced by the downstream players in DNA replication, recombination, and repair that bind ssDNA with much lower affinity. Recent studies, and in particular single-molecule observations of RPA-ssDNA interactions, led to the development of a new model for the ssDNA handoff from RPA to a specific downstream factor where not only stability and structural rearrangements but also RPA conformational dynamics guide the ssDNA handoff. Here we will review the current knowledge of the RPA structure, its dynamic interaction with ssDNA, and how RPA conformational dynamics may be influenced by posttranslational modification and proteins that interact with RPA, as well as how RPA dynamics may be harnessed in cellular decision making.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 5","pages":"482-507"},"PeriodicalIF":6.5,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821911/pdf/nihms-1648328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38318859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mrinmoyee Majumder, Roger H Johnson, Viswanathan Palanisamy
{"title":"Fragile X-related protein family: a double-edged sword in neurodevelopmental disorders and cancer.","authors":"Mrinmoyee Majumder, Roger H Johnson, Viswanathan Palanisamy","doi":"10.1080/10409238.2020.1810621","DOIUrl":"https://doi.org/10.1080/10409238.2020.1810621","url":null,"abstract":"<p><p>The fragile X-related (FXR) family proteins FMRP, FXR1, and FXR2 are RNA binding proteins that play a critical role in RNA metabolism, neuronal plasticity, and muscle development. These proteins share significant homology in their protein domains, which are functionally and structurally similar to each other. FXR family members are known to play an essential role in causing fragile X mental retardation syndrome (FXS), the most common genetic form of autism spectrum disorder. Recent advances in our understanding of this family of proteins have occurred in tandem with discoveries of great importance to neurological disorders and cancer biology <i>via</i> the identification of their novel RNA and protein targets. Herein, we review the FXR family of proteins as they pertain to FXS, other mental illnesses, and cancer. We emphasize recent findings and analyses that suggest contrasting functions of this protein family in FXS and tumorigenesis based on their expression patterns in human tissues. Finally, we discuss current gaps in our knowledge regarding the FXR protein family and their role in FXS and cancer and suggest future studies to facilitate bench to bedside translation of the findings.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 5","pages":"409-424"},"PeriodicalIF":6.5,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2020.1810621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38338204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Moonlighting glyceraldehyde-3-phosphate dehydrogenase: posttranslational modification, protein and nucleic acid interactions in normal cells and in human pathology.","authors":"Michael A Sirover","doi":"10.1080/10409238.2020.1787325","DOIUrl":"https://doi.org/10.1080/10409238.2020.1787325","url":null,"abstract":"<p><p>Moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibits multiple functions separate and distinct from its historic role in energy production. Further, it exhibits dynamic changes in its subcellular localization which is an a priori requirement for its multiple activities. Separately, moonlighting GAPDH may function in the pathology of human disease, involved in tumorigenesis, diabetes, and age-related neurodegenerative disorders. It is suggested that moonlighting GAPDH function may be related to specific modifications of its protein structure as well as the formation of GAPDH protein: protein or GAPDH protein: nucleic acid complexes.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 4","pages":"354-371"},"PeriodicalIF":6.5,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2020.1787325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38143617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rashmi S Hegde, Kaushik Roychoudhury, Ram Naresh Pandey
{"title":"The multi-functional eyes absent proteins.","authors":"Rashmi S Hegde, Kaushik Roychoudhury, Ram Naresh Pandey","doi":"10.1080/10409238.2020.1796922","DOIUrl":"10.1080/10409238.2020.1796922","url":null,"abstract":"<p><p>The Eyes Absent (EYA) proteins are the only known instance of a single polypeptide housing the following three separable biochemical activities: tyrosine phosphatase, threonine phosphatase, and transactivation. This uniquely positions the EYAs to participate in both transcriptional regulation and signal transduction pathways. But it also complicates the assignment of biological roles to individual biochemical activities through standard loss-of-function experiments. Nevertheless, there is an emerging literature linking developmental and pathological functions with the various EYA activities, and a growing list of disease states that might benefit from EYA-targeted therapeutics. There also remain multiple unresolved issues with significant implications for our understanding of how the EYAs might impact such ubiquitous signaling cascades as the MYC and Notch pathways. This review will describe the unique juxtaposition of biochemical activities in the EYAs, their interaction with signaling pathways and cellular processes, emerging evidence of roles in disease states, and the feasibility of therapeutic targeting of individual EYA activities. We will focus on the phosphatase activities of the vertebrate EYA proteins and will examine the current state of knowledge regarding: • substrates and signaling pathways affected by the EYA tyrosine phosphatase activity; • modes of regulation of the EYA tyrosine phosphatase activity; • signaling pathways that implicate the threonine phosphatase activity of the EYAs including a potential interaction with PP2A-B55α; • the interplay between the two phosphatase activities and the transactivation function of the EYAs; • disease states associated with the EYAs and the current state of development of EYA-targeted therapeutics.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"55 4","pages":"372-385"},"PeriodicalIF":6.5,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727457/pdf/nihms-1648379.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38206742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}