scholarly journals Same agent, different messages: insight into transcriptional regulation by SIN3 isoforms

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashlesha Chaubal ◽  
Lori A. Pile
2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Yang Zhang ◽  
Jun Yang ◽  
Guangchun Bai

ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide bacteria and archaea with adaptive immunity to specific DNA invaders. Mycobacterium tuberculosis encodes a type III CRISPR-Cas system that has not been experimentally explored. In this study, we found that the CRISPR-Cas systems of both M. tuberculosis and Mycobacterium bovis BCG were highly upregulated by deletion of Rv2837c ( cnpB ), which encodes a multifunctional protein that hydrolyzes cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and nanoRNAs (short oligonucleotides of 5 or fewer residues). By using genetic and biochemical approaches, we demonstrated that the CnpB-controlled transcriptional regulation of the CRISPR-Cas system is mediated by an Orn-like activity rather than by hydrolyzing the cyclic dinucleotides. Additionally, our results revealed that tuberculosis (TB) complex mycobacteria are functional in processing CRISPR RNAs (crRNAs), which are also more abundant in the Δ cnpB strain than in the parent strain. The elevated crRNA levels in the Δ cnpB strain could be partially reduced by expressing Escherichia coli orn . Our findings provide new insight into transcriptional regulation of bacterial CRISPR-Cas systems. IMPORTANCE Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide adaptive immunity to specific DNA invaders. M. tuberculosis encodes a type III CRISPR-Cas system that has not been experimentally explored. In this study, we first demonstrated that the CRISPR-Cas systems in tuberculosis (TB) complex mycobacteria are functional in processing CRISPR RNAs (crRNAs). We also showed that Rv2837c (CnpB) controls the expression of the CRISPR-Cas systems in TB complex mycobacteria through an oligoribonuclease (Orn)-like activity, which is very likely mediated by nanoRNA. Since little is known about regulation of CRISPR-Cas systems, our findings provide new insight into transcriptional regulation of bacterial CRISPR-Cas systems.


2020 ◽  
Vol 56 (64) ◽  
pp. 9134-9137
Author(s):  
Nesreen Hamad ◽  
Hiroki Watanabe ◽  
Takayuki Uchihashi ◽  
Riki Kurokawa ◽  
Takashi Nagata ◽  
...  

Conformational change of FUS protein detected by AFM upon binding of non-coding RNA provides a mechanistic insight into transcriptional regulation.


2012 ◽  
Vol 33 (3) ◽  
pp. 498-513 ◽  
Author(s):  
R. Montgomery Gill ◽  
Timothy V. Gabor ◽  
Amber L. Couzens ◽  
Michael P. Scheid

ABSTRACTCell division control protein A7 (CDCA7) is a recently identified target of MYC-dependent transcriptional regulation. We have discovered that CDCA7 associates with MYC and that this association is modulated in a phosphorylation-dependent manner. The prosurvival kinase AKT phosphorylates CDCA7 at threonine 163, promoting binding to 14-3-3, dissociation from MYC, and sequestration to the cytoplasm. Upon serum withdrawal, induction of CDCA7 expression in the presence of MYC sensitized cells to apoptosis, whereas CDCA7 knockdown reduced MYC-dependent apoptosis. The transformation of fibroblasts by MYC was reduced by coexpression of CDCA7, while the non-MYC-interacting protein Δ(156–187)-CDCA7 largely inhibited MYC-induced transformation. These studies provide insight into a new mechanism by which AKT signaling to CDCA7 could alter MYC-dependent growth and transformation, contributing to tumorigenesis.


2017 ◽  
Author(s):  
Chinmay J Shukla ◽  
Alexandra L McCorkindale ◽  
Chiara Gerhardinger ◽  
Keegan D Korthauer ◽  
Moran N Cabili ◽  
...  

SummaryOne of the biggest surprises since the sequencing of the human genome has been the discovery of thousands of long noncoding RNAs (lncRNAs)1–6. Although lncRNAs and mRNAs are similar in many ways, they differ with lncRNAs being more nuclear-enriched and in several cases exclusively nuclear7,8. Yet, the RNA-based sequences that determine nuclear localization remain poorly understood9–11. Towards the goal of systematically dissecting the lncRNA sequences that impart nuclear localization, we developed a massively parallel reporter assay (MPRA). Unlike previous MPRAs12–15 that determine motifs important for transcriptional regulation, we have modified this approach to identify sequences sufficient for RNA nuclear enrichment for 38 human lncRNAs. Using this approach, we identified 109 unique, conserved nuclear enrichment regions, originating from 29 distinct lncRNAs. We also discovered two shorter motifs within our nuclear enrichment regions. We further validated the sufficiency of several regions to impart nuclear localization by single molecule RNA fluorescence in situ hybridization (smRNA-FISH). Taken together, these results provide a first systematic insight into the sequence elements responsible for the nuclear enrichment of lncRNA molecules.


2019 ◽  
Vol 93 ◽  
pp. 597-611 ◽  
Author(s):  
N.D. Janson ◽  
Nilojan Jehanathan ◽  
Sumi Jung ◽  
Thanthrige Thiunuwan Priyathilaka ◽  
Bo-Hye Nam ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document