scholarly journals Co-Transcriptional RNA Processing in Plants: Exploring from the Perspective of Polyadenylation

2021 ◽  
Vol 22 (7) ◽  
pp. 3300
Author(s):  
Jing Yang ◽  
Ying Cao ◽  
Ligeng Ma
Keyword(s):  
Rna Polymerase Ii ◽  
Rna Processing ◽  
Messenger Rna ◽  
Environmental Changes ◽  
Alternative Polyadenylation ◽  
Protein Coding ◽  
Limited Mobility ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Spatial Environment

Most protein-coding genes in eukaryotes possess at least two poly(A) sites, and alternative polyadenylation is considered a contributing factor to transcriptomic and proteomic diversity. Following transcription, a nascent RNA usually undergoes capping, splicing, cleavage, and polyadenylation, resulting in a mature messenger RNA (mRNA); however, increasing evidence suggests that transcription and RNA processing are coupled. Plants, which must produce rapid responses to environmental changes because of their limited mobility, exhibit such coupling. In this review, we summarize recent advances in our understanding of the coupling of transcription with RNA processing in plants, and we describe the possible spatial environment and important proteins involved. Moreover, we describe how liquid–liquid phase separation, mediated by the C-terminal domain of RNA polymerase II and RNA processing factors with intrinsically disordered regions, enables efficient co-transcriptional mRNA processing in plants.

scholarly journals Transient DNA Binding Induces RNA Polymerase II Compartmentalization During Herpesviral Infection Distinct From Phase Separation

2018 ◽  
Author(s):  
David T McSwiggen ◽  
Anders S Hansen ◽  
Hervé Marie-Nelly ◽  
Sheila Teves ◽  
Alec B Heckert ◽  
...  
Keyword(s):  
Phase Separation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Protein Interactions ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Pol Ii ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Simplex Virus

SummaryDuring lytic infection, Herpes Simplex Virus 1 generates replication compartments (RCs) in host nuclei that efficiently recruit protein factors, including host RNA Polymerase II (Pol II). Pol II and other cellular factors form hubs in uninfected cells that are proposed to phase separate via multivalent protein-protein interactions mediated by their intrinsically disordered regions. Using a battery of live cell microscopic techniques, we show that although RCs superficially exhibit many characteristics of phase separation, the recruitment of Pol II instead derives from nonspecific interactions with the viral DNA. We find that the viral genome remains nucleosome-free, profoundly affecting the way Pol II explores RCs by causing it to repetitively visit nearby binding sites, thereby creating local Pol II accumulations. This mechanism, distinct from phase separation, allows viral DNA to outcompete host DNA for cellular proteins. Our work provides new insights into the strategies used to create local molecular hubs in cells.

scholarly journals Novel LOTUS-domain proteins are organizational hubs that recruit C. elegans Vasa to germ granules

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Patricia Giselle Cipriani ◽  
Olivia Bay ◽  
John Zinno ◽  
Michelle Gutwein ◽  
Hin Hark Gan ◽  
...  
Keyword(s):  
Rna Processing ◽  
Germ Line ◽  
Temperature Sensitive ◽  
Developmental Transitions ◽  
P Granules ◽  
C Elegans ◽  
Intrinsically Disordered ◽  
Meiotic Progression ◽  
Intrinsically Disordered Regions ◽  
Granule Growth

We describe MIP-1 and MIP-2, novel paralogous C. elegans germ granule components that interact with the intrinsically disordered MEG-3 protein. These proteins promote P granule condensation, form granules independently of MEG-3 in the postembryonic germ line, and balance each other in regulating P granule growth and localization. MIP-1 and MIP-2 each contain two LOTUS domains and intrinsically disordered regions and form homo- and heterodimers. They bind and anchor the Vasa homolog GLH-1 within P granules and are jointly required for coalescence of MEG-3, GLH-1, and PGL proteins. Animals lacking MIP-1 and MIP-2 show temperature-sensitive embryonic lethality, sterility, and mortal germ lines. Germline phenotypes include defects in stem cell self-renewal, meiotic progression, and gamete differentiation. We propose that these proteins serve as scaffolds and organizing centers for ribonucleoprotein networks within P granules that help recruit and balance essential RNA processing machinery to regulate key developmental transitions in the germ line.

scholarly journals Computational Characterization of the mtORF of Pocilloporid Corals: Insights into Protein Structure and Function in Stylophora Lineages from Contrasting Environments

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 324
Author(s):  
Banguera-Hinestroza ◽  
Ferrada ◽  
Sawall ◽  
Flot
Keyword(s):  
Red Sea ◽  
Metal Binding ◽  
Tandem Repeats ◽  
Environmental Changes ◽  
Transmembrane Protein ◽  
Domain Architecture ◽  
Thermal Adaptation ◽  
Functional Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae and has been used since then as an effective barcode for these corals. Recently, mtORF sequencing revealed the existence of two differentiated Stylophora lineages occurring in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C). In the endemic Red Sea lineage RS_LinB, the mtORF and the heat shock protein gene hsp70 uncovered similar phylogeographic patterns strongly correlated with environmental variations. This suggests that the mtORF too might be involved in thermal adaptation. Here, we used computational analyses to explore the features and putative function of this mtORF. In particular, we tested the likelihood that this gene encodes a functional protein and whether it may play a role in adaptation. Analyses of full mitogenomes showed that the mtORF originated in the common ancestor of Madracis and other pocilloporids, and that it encodes a transmembrane protein differing in length and domain architecture among genera. Homology-based annotation and the relative conservation of metal-binding sites revealed traces of an ancient hydrolase catalytic activity. Furthermore, signals of pervasive purifying selection, lack of stop codons in 1830 sequences analyzed, and a codon-usage bias similar to that of other mitochondrial genes indicate that the protein is functional, i.e., not a pseudogene. Other features, such as intrinsically disordered regions, tandem repeats, and signals of positive selection particularly in Stylophora RS_LinB populations, are consistent with a role of the mtORF in adaptive responses to environmental changes.

scholarly journals DNA Processing in The Context of Non-Coding Transcription

2020 ◽  
Author(s):  
Uthra Gowthaman ◽  
Desiré García-Pichardo ◽  
Yu Jin ◽  
Isabel Schwarz ◽  
Sebastian Marquardt
Keyword(s):  
Rna Polymerase Ii ◽  
Dna Sequences ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Biological Significance ◽  
Protein Coding ◽  
Non Coding Rna ◽  
Functional Dna ◽  
The Impact ◽  
Dna Processing

RNA polymerase II (RNAPII) frequently transcribes non-protein coding DNA sequences in eukaryotic genomes into long non-coding RNA (lncRNA). Here, we focus on the impact of the act of lncRNA transcription on nearby functional DNA units. Distinct molecular mechanisms linked to the position of lncRNA relative to the coding gene illustrate how non-coding transcription controls gene expression. We review the biological significance of the act of lncRNA transcription on DNA processing, highlighting common themes, such as mediating cellular responses to environmental changes. This review presents the background in chromatin signaling to appreciate examples in different organisms where we can interpret functions of non-coding DNA through the act of RNAPII transcription.

scholarly journals Beyond Microsatellite Instability: Intrinsic Disorder as a Potential Link Between Protein Short Tandem Repeats and Cancer

2021 ◽  
Vol 1 ◽  
Author(s):  
Max A. Verbiest ◽  
Matteo Delucchi ◽  
Tugce Bilgin Sonay ◽  
Maria Anisimova
Keyword(s):  
Amino Acids ◽  
Microsatellite Instability ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Disordered Proteins ◽  
Future Research ◽  
Protein Coding ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Short Tandem

Short tandem repeats (STRs) are abundant in genomic sequences and are known for comparatively high mutation rates; STRs therefore are thought to be a potent source of genetic diversity. In protein-coding sequences STRs primarily encode disorder-promoting amino acids and are often located in intrinsically disordered regions (IDRs). STRs are frequently studied in the scope of microsatellite instability (MSI) in cancer, with little focus on the connection between protein STRs and IDRs. We believe, however, that this relationship should be explicitly included when ascertaining STR functionality in cancer. Here we explore this notion using all canonical human proteins from SwissProt, wherein we detected 3,699 STRs. Over 80% of these consisted completely of disorder promoting amino acids. 62.1% of amino acids in STR sequences were predicted to also be in an IDR, compared to 14.2% for non-repeat sequences. Over-representation analysis showed STR-containing proteins to be primarily located in the nucleus where they perform protein- and nucleotide-binding functions and regulate gene expression. They were also enriched in cancer-related signaling pathways. Furthermore, we found enrichments of STR-containing proteins among those correlated with patient survival for cancers derived from eight different anatomical sites. Intriguingly, several of these cancer types are not known to have a MSI-high (MSI-H) phenotype, suggesting that protein STRs play a role in cancer pathology in non MSI-H settings. Their intrinsic link with IDRs could therefore be an attractive topic of future research to further explore the role of STRs and IDRs in cancer. We speculate that our observations may be linked to the known dosage-sensitivity of disordered proteins, which could hint at a concentration-dependent gain-of-function mechanism in cancer for proteins containing STRs and IDRs.

Role of the C-terminal domain of RNA polymerase II in expression of small nuclear RNA genes

2008 ◽  
Vol 36 (3) ◽  
pp. 537-539 ◽  
Author(s):  
Sylvain Egloff ◽  
Shona Murphy
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rna Processing ◽  
Repeat Unit ◽  
Small Nuclear Rna ◽  
Protein Coding ◽  
Pol Ii ◽  
Terminal Domain ◽  
Covalent Modifications

Pol II (RNA polymerase II) transcribes the genes encoding proteins and non-coding snRNAs (small nuclear RNAs). The largest subunit of Pol II contains a distinctive CTD (C-terminal domain) comprising a repetitive heptad amino acid sequence, Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. This domain is now known to play a major role in the processes of transcription and co-transcriptional RNA processing in expression of both snRNA and protein-coding genes. The heptapeptide repeat unit can be extensively modified in vivo and covalent modifications of the CTD during the transcription cycle result in the ordered recruitment of RNA-processing factors. The most studied modifications are the phosphorylation of the serine residues in position 2 and 5 (Ser2 and Ser5), which play an important role in the co-transcriptional processing of both mRNA and snRNA. An additional, recently identified CTD modification, phosphorylation of the serine residue in position 7 (Ser7) of the heptapeptide, is however specifically required for expression of snRNA genes. These findings provide interesting insights into the control of gene-specific Pol II function.

scholarly journals Cloud Prediction of Protein Structure and Function with PredictProtein for Debian

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
László Kaján ◽  
Guy Yachdav ◽  
Esmeralda Vicedo ◽  
Martin Steinegger ◽  
Milot Mirdita ◽  
...  
Keyword(s):  
High Performance ◽  
Solvent Accessibility ◽  
Protein Coding ◽  
Nuclear Localization Signals ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Coding Regions ◽  
Standard Set ◽  
And Function ◽  
Performance Computing

We report the release of PredictProtein for the Debian operating system and derivatives, such as Ubuntu, Bio-Linux, and Cloud BioLinux. The PredictProtein suite is available as a standard set of open source Debian packages. The release covers the most popular prediction methods from the Rost Lab, including methods for the prediction of secondary structure and solvent accessibility (profphd), nuclear localization signals (predictnls), and intrinsically disordered regions (norsnet). We also present two case studies that successfully utilize PredictProtein packages for high performance computing in the cloud: the first analyzes protein disorder for whole organisms, and the second analyzes the effect of all possible single sequence variants in protein coding regions of the human genome.

scholarly journals Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
David Trombley McSwiggen ◽  
Anders S Hansen ◽  
Sheila S Teves ◽  
Hervé Marie-Nelly ◽  
Yvonne Hao ◽  
...  
Keyword(s):  
Phase Separation ◽  
Dna Binding ◽  
Rna Polymerase Ii ◽  
Protein Interactions ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Pol Ii ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Simplex Virus

RNA Polymerase II (Pol II) and transcription factors form concentrated hubs in cells via multivalent protein-protein interactions, often mediated by proteins with intrinsically disordered regions. During Herpes Simplex Virus infection, viral replication compartments (RCs) efficiently enrich host Pol II into membraneless domains, reminiscent of liquid-liquid phase separation. Despite sharing several properties with phase-separated condensates, we show that RCs operate via a distinct mechanism wherein unrestricted nonspecific protein-DNA interactions efficiently outcompete host chromatin, profoundly influencing the way DNA-binding proteins explore RCs. We find that the viral genome remains largely nucleosome-free, and this increase in accessibility allows Pol II and other DNA-binding proteins to repeatedly visit nearby DNA binding sites. This anisotropic behavior creates local accumulations of protein factors despite their unrestricted diffusion across RC boundaries. Our results reveal underappreciated consequences of nonspecific DNA binding in shaping gene activity, and suggest additional roles for chromatin in modulating nuclear function and organization.

scholarly journals Phase separation-deficient TDP43 remains functional in splicing

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hermann Broder Schmidt ◽  
Ariana Barreau ◽  
Rajat Rohatgi
Keyword(s):  
Phase Separation ◽  
Rna Processing ◽  
Material Properties ◽  
Reporter Assay ◽  
Evolutionary Sequence ◽  
Processing Factor ◽  
Phase Dynamics ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Sequence Complexity

Abstract Intrinsically disordered regions (IDRs) are often fast-evolving protein domains of low sequence complexity that can drive phase transitions and are commonly found in many proteins associated with neurodegenerative diseases, including the RNA processing factor TDP43. Yet, how phase separation contributes to the physiological functions of TDP43 in cells remains enigmatic. Here, we combine systematic mutagenesis guided by evolutionary sequence analysis with a live-cell reporter assay of TDP43 phase dynamics to identify regularly-spaced hydrophobic motifs separated by flexible, hydrophilic segments in the IDR as a key determinant of TDP43 phase properties. This heuristic framework allows customization of the material properties of TDP43 condensates to determine effects on splicing function. Remarkably, even a mutant that fails to phase-separate at physiological concentrations can still efficiently mediate the splicing of a quantitative, single-cell splicing reporter and endogenous targets. This suggests that the ability of TDP43 to phase-separate is not essential for its splicing function.

scholarly journals The cohesin regulator Stag1 promotes cell plasticity through heterochromatin regulation

2021 ◽  
Author(s):  
Dubravka Pezic ◽  
Sam Weeks ◽  
Wazeer Varsally ◽  
Pooran S. Dewari ◽  
Steven Pollard ◽  
...  
Keyword(s):  
Es Cells ◽  
Repetitive Sequences ◽  
Embryonic Stem ◽  
Protein Isoforms ◽  
Cellular Plasticity ◽  
Cell Plasticity ◽  
Protein Coding ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Nucleolar Function

SUMMARYFundamental biological processes such as embryo development and stem cell control rely on cellular plasticity. We present a role for the cohesin regulator, Stag1 in cellular plasticity control via heterochromatin regulation. Stag1 localises to heterochromatin domains and repetitive sequences in embryonic stem (ES) cells and contains intrinsically disordered regions in its divergent terminal ends which promote heterochromatin compaction. ES cells express Stag1 protein isoforms lacking the disordered ends and fluctuations in isoform abundance skews the cell state continuum towards increased differentiation or reprogramming. The role for Stag1 in heterochromatin condensates and nucleolar function is dependent on its unique N-terminus. Stag1NΔ ESCs have decompacted chromatin and reprogram towards totipotency, exhibiting MERVL derepression, reduced nucleolar transcription and decreased translation. Our results move beyond protein-coding gene regulation via chromatin loops into a new role for Stag1 in heterochromatin and nucleolar function and offer fresh perspectives on its contribution to cell identity and disease.

Sign in / Sign up

Export Citation Format

Share Document