scholarly journals The Structure-to-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and their Contributions to Viral Pathogenesis

2018 ◽  
Author(s):  
Gabriela Chavez Calvillo ◽  
Sarah Martin ◽  
Chad Hamm ◽  
Joanna Sztuba-Solinska
Keyword(s):  
Viral Gene Expression ◽  
Viral Pathogenesis ◽  
Viral Gene ◽  
Cellular Processes ◽  
Messenger Molecules ◽  
Non Coding Rnas ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Pleiotropic Functions

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

scholarly journals The Structure-To-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and Their Contributions to Viral Pathogenesis

2018 ◽  
Vol 4 (4) ◽  
pp. 24 ◽  
Author(s):  
Gabriela Chavez-Calvillo ◽  
Sarah Martin ◽  
Chad Hamm ◽  
Joanna Sztuba-Solinska
Keyword(s):  
Viral Gene Expression ◽  
Viral Pathogenesis ◽  
Viral Gene ◽  
Cellular Processes ◽  
Messenger Molecules ◽  
Non Coding Rnas ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Pleiotropic Functions

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. These lncRNAs allow for the virus to escape cytosolic surveillance, sequester, and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis, and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

Protein-RNA interactome analysis reveals wide association of KSHV ORF57 with host non-coding RNAs and polysomes

2021 ◽  
Author(s):  
Beatriz Alvarado-Hernandez ◽  
Yanping Ma ◽  
Nishi R. Sharma ◽  
Vladimir Majerciak ◽  
Alexei Lobanov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Splicing ◽  
Rna Binding ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
28S Rrna ◽  
Protein Coding ◽  
Infected Cells ◽  
Non Coding Rnas ◽  
Rna Interaction

Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF57 is an RNA-binding post-transcriptional regulator. We recently applied an affinity-purified anti-ORF57 antibody to conduct ORF57-CLIP (Cross-linking Immunoprecipitation) in combination with RNA-sequencing (CLIP-seq) and analyzed the genome-wide host RNA transcripts in association with ORF57 in BCBL-1 cells with lytic KSHV infection. Mapping of the CLIPed RNA reads to the human genome (GRCh37) revealed that most of the ORF57-associated RNA reads were from rRNAs. The remaining RNA reads mapped to several classes of host non-coding and protein-coding mRNAs. We found ORF57 binds and regulates expression of a subset of host lncRNAs, including LINC00324, LINC00355, and LINC00839 which are involved in cell growth. ORF57 binds snoRNAs responsible for 18S and 28S rRNA modifications, but does not interact with fibrillarin and NOP58. We validated ORF57 interactions with 67 snoRNAs by ORF57-RNA immunoprecipitation (RIP)-snoRNA-array assays. Most of the identified ORF57 rRNA binding sites (BS) overlap with the sites binding snoRNAs. We confirmed ORF57-snoRA71B RNA interaction in BCBL-1 cells by ORF57-RIP and Northern blot analyses using a 32 P-labeled oligo probe from the 18S rRNA region complementary to snoRA71B. Using RNA oligos from the rRNA regions that ORF57 binds for oligo pulldown-Western blot assays, we selectively verified ORF57 interactions with 5.8S and 18S rRNAs. Polysome profiling revealed that ORF57 associates with both monosomes and polysomes and its association with polysomes increases PABPC1 binding to, but prevent Ago2 from polysomes. Our data indicate a functional correlation with ORF57 binding and suppression of Ago2 activities for ORF57 promotion of gene expression. Significance As an RNA-binding protein, KSHV ORF57 regulates RNA splicing, stability, and translation and inhibits host innate immunity by blocking the formation of RNA granules in virus infected cells. In this report, ORF57 was found to interact many host non-coding RNAs, including lncRNAs, snoRNAs and ribosomal RNAs to carry out additional unknown functions. ORF57 binds a group of lncRNAs via the identified RNA motifs by ORF57 CLIP-seq to regulate their expression. ORF57 associates with snoRNAs independently of fibrillarin and NOP58 proteins, and with ribosomal RNA in the regions that commonly bind snoRNAs. Knockdown of fibrillarin expression decreases the expression of snoRNAs and CDK4, but not affect viral gene expression. More importantly, we found that ORF57 binds translationally active polysomes and enhances PABPC-1 but prevents Ago2 association with polysomes. Data provide a compelling evidence on how ORF57 in KSHV infected cells might regulate protein synthesis by blocking Ago2’s hostile activities on translation.

Single-Molecule Force Spectroscopy of Transmembrane β-Barrel Proteins

2018 ◽  
Vol 11 (1) ◽  
pp. 375-395 ◽  
Author(s):  
Johannes Thoma ◽  
K. Tanuj Sapra ◽  
Daniel J. Müller
Keyword(s):  
Single Molecule ◽  
Force Spectroscopy ◽  
General Mechanism ◽  
Dynamic Mode ◽  
Single Molecule Force Spectroscopy ◽  
Force Relaxation ◽  
Sequential Unfolding ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function

Single-molecule force spectroscopy (SMFS) has been widely applied to study the mechanical unfolding and folding of transmembrane proteins. Here, we review the recent progress in characterizing bacterial and human transmembrane β-barrel proteins by SMFS. First, we describe the mechanical unfolding of transmembrane β-barrels, which follows a general mechanism dictated by the sequential unfolding and extraction of individual β-strands and β-hairpins from membranes. Upon force relaxation, the unfolded polypeptide can insert stepwise into the membrane as single β-strands or β-hairpins to fold as the native β-barrel. The refolding can be followed at a high spatial and temporal resolution, showing that small β-barrels are able to fold without assistance, whereas large and complex β-barrels require chaperone cofactors. Applied in the dynamic mode, SMFS can quantify the kinetic and mechanical properties of single β-hairpins and reveal complementary insight into the membrane protein structure and function relationship. We further outline the challenges that SMFS experiments must overcome for a comprehensive understanding of the folding and function of transmembrane β-barrel proteins.

In Silico Identification for α-Amino-ε-Caprolactam Racemases by Using Information on the Structure and Function Relationship

2015 ◽  
Vol 176 (5) ◽  
pp. 1303-1314 ◽  
Author(s):  
Wisarut Payoungkiattikun ◽  
Seiji Okazaki ◽  
Shogo Nakano ◽  
Atsutoshi Ina ◽  
Aran H-Kittikun ◽  
...  
Keyword(s):  
In Silico ◽  
Structure And Function ◽  
In Silico Identification ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function

Structure and Function Relationship of Murine Insulin-like Peptide 5 (INSL5): Free C-Terminus Is Essential for RXFP4 Receptor Binding and Activation

Biochemistry ◽  
2011 ◽  
Vol 50 (39) ◽  
pp. 8352-8361 ◽  
Author(s):  
Alessia Belgi ◽  
Mohammed A. Hossain ◽  
Fazel Shabanpoor ◽  
Linda Chan ◽  
Suode Zhang ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structure And Function ◽  
C Terminus ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of
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