Long noncoding RNA (lincRNA), a new paradigm in gene expression control

2016 ◽  
Vol 17 (2-3) ◽  
pp. 135-143 ◽  
Author(s):  
Emre Deniz ◽  
Batu Erman
2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Jessica Rea ◽  
Valentina Menci ◽  
Paolo Tollis ◽  
Tiziana Santini ◽  
Alexandros Armaos ◽  
...  

Abstract Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.


2019 ◽  
Vol 8 (5) ◽  
pp. 597-612 ◽  
Author(s):  
Daniela F. Rodrigues ◽  
Vera M. Costa ◽  
Ricardo Silvestre ◽  
Maria L. Bastos ◽  
Félix Carvalho

Abstract The transcriptome is the complete set of transcripts in a cell or tissue and includes ribosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and regulatory noncoding RNA. At steady-state, the transcriptome results from a compensatory variation of the transcription and decay rate to maintain the RNA concentration constant. RNA transcription constitutes the first stage in gene expression, and thus is a major and primary mode of gene expression control. Nevertheless, regulation of RNA decay is also a key factor in gene expression control, involving either selective RNA stabilization or enhanced degradation. Transcriptome analysis allows the identification of gene expression alterations, providing new insights regarding the pathways and mechanisms involved in physiological and pathological processes. Upon perturbation of cell homeostasis, rapid changes in gene expression are required to adapt to new conditions. Thus, to better understand the regulatory mechanisms associated with gene expression alterations, it is vital to acknowledge the relative contribution of RNA synthesis and decay to the transcriptome. To the toxicology field, the study of gene expression regulation mechanisms can help identify the early and mechanistic relevant cellular events associated with a particular response. This review aims to provide a critical comparison of the available methods used to analyze the contribution of RNA transcription and decay to gene expression dynamics. Notwithstanding, an integration of the data obtained is necessary to understand the entire repercussions of gene transcription changes at a system-level. Thus, a brief overview of the methods available for the integration and analysis of the data obtained from transcriptome analysis will also be provided.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.


Nature ◽  
2011 ◽  
Vol 473 (7347) ◽  
pp. 337-342 ◽  
Author(s):  
Björn Schwanhäusser ◽  
Dorothea Busse ◽  
Na Li ◽  
Gunnar Dittmar ◽  
Johannes Schuchhardt ◽  
...  

2004 ◽  
Vol 22 (7) ◽  
pp. 824-826 ◽  
Author(s):  
Francine B Perler

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