Premature termination of<i>GAT1</i>transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production

et al. 2018

Microbiol Mol Biol Rev

Nitrogen is one of the most important essential nutrient sources for biogenic activities. Regulation of nitrogen metabolism in microorganisms is complicated and elaborate. For this review, the yeast was chosen to demonstrate the regulatory mechanism of nitrogen metabolism because of its relative clear genetic background. Current opinions on the regulation processes of nitrogen metabolism in, including nitrogen sensing, transport, and catabolism, are systematically reviewed. Two major upstream signaling pathways, the Ssy1-Ptr3-Ssy5 sensor system and the target of rapamycin pathway, which are responsible for sensing extracellular and intracellular nitrogen, respectively, are discussed. The ubiquitination of nitrogen transporters, which is the most general and efficient means for controlling nitrogen transport, is also summarized. The following metabolic step, nitrogen catabolism, is demonstrated at two levels: the transcriptional regulation process related to GATA transcriptional factors and the translational regulation process related to the general amino acid control pathway. The interplay between nitrogen regulation and carbon regulation is also discussed. As a model system, understanding the meticulous process by which nitrogen metabolism is regulated in not only could facilitate research on global regulation mechanisms and yeast metabolic engineering but also could provide important insights and inspiration for future studies of other common microorganisms and higher eukaryotic cells.

Section: Regulation Of Gln3 and Gat1mentioning

confidence: 99%

Section: Regulation Of Gln3 and Gat1mentioning

confidence: 99%

Regulation of Sensing, Transportation, and Catabolism of Nitrogen Sources in Saccharomyces cerevisiae

Zhang

et al. 2018

Microbiol Mol Biol Rev

“…The key GATA factors involved in NCR signaling are two activators (Gln3 and Gat1/Nil1) and two repressors (Gzf3/Nil2/Deh1 and Dal80/Uga43) [ 33 – 38 ]. In a perfect feedback loop, the expression of DAL80 and GAT1 is also NCR-sensitive, which implies cross- and autogenous regulations of the GATA factors in the NCR mechanisms [ 38 – 41 ]. Under nitrogen limitation, expression of DAL80 is highly induced [ 35 ], and Dal80 enters the nucleus where it competes with the two GATA activators for the same binding sites [ 20 , 39 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes

et al. 2019

Self Cite

GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes.

“…It has been shown that the expression of heterologous gene can be suppressed due to PCPA in coding regions ( Diehn et al, 1998 ; Tokuoka et al, 2008 ). PCPA also occurs in coding regions of endogenous genes in both yeast and human ( van Hoof et al, 2002 ; Frischmeyer et al, 2002 ; Georis et al, 2015 ). Importantly, many poly(A) sites have been mapped to coding regions using poly(A) sequencing methods ( Jan et al, 2011 ; Liu et al, 2017b ; Ulitsky et al, 2012 ; Yang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Codon usage biases co-evolve with transcription termination machinery to suppress premature cleavage and polyadenylation

Dang

et al. 2018

eLife

Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here, we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and abolishment of full-length mRNA. PTT is a wide-spread phenomenon in Neurospora, and there is a strong negative correlation between codon usage bias and PTT events. Rare codons lead to the formation of putative poly(A) signals and PTT. A similar role for codon usage bias was also observed in mouse cells. Together, these results suggest that codon usage biases co-evolve with the transcription termination machinery to suppress premature termination of transcription and thus allow for optimal gene expression.