Connections between Transcription Downstream of Genes and cis-SAGe Chimeric RNA

Chwalenia, Katarzyna; Qin, Fujun; Singh, Sandeep; Tangtrongstittikul, Panjapon; Li, Hui

doi:10.3390/genes8110338

Cited by 6 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the system can be used to assess environmental factors, viral infections, and even to screen small molecule inhibitors. For example, a recent study revealed the induction of transcriptions downstream of genes (DoGs) under osmotic stress (18,50,51), which may contribute to the regulation of cis-SAGe chimeric RNAs. We built in additional RNA and protein destabilization sequences, ideal for studying the effect of such osmotic stress, which often requires a rapid readout within a few hours.…”

Section: Discussionmentioning

confidence: 99%

A cell-based splicing reporter system to identify regulators of cis-splicing between adjacent genes

Chwalenia

Qin

Singh

2018

Nucleic Acids Research

Self Cite

View full text Add to dashboard Cite

Chimeric RNAs generated by cis-splicing between adjacent genes (cis-SAGe) are increasingly recognized as a widespread phenomenon. These chimeric messenger RNAs are present in normal human cells, and are also detected in various cancers. The mechanisms for how this group of chimeras is formed are not yet clear, in part due to the lack of a tractable system for their experimental investigation. Here we developed a fast, easy and versatile cell-based reporter system to identify regulators of cis-SAGe. The reporter, consisting of four main cassettes, simultaneously measures the effects of a candidate regulator on cis-SAGe and canonical splicing. Using this cell-based assay, we screened 102 candidate factors involved in RNA pol II cleavage and termination, elongation, splicing, alternative splicing and R-loop formation. We discovered that two factors, SRRM1 and SF3B1, affect not only cis-SAGe chimeras, but also other types of chimeric RNAs in a genome-wide fashion. This system can be used for studying trans-acting factors and cis-acting sequence elements and factors, as well as for screening small molecule inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

A cell-based splicing reporter system to identify regulators of cis-splicing between adjacent genes

Chwalenia

Qin

Singh

2018

Nucleic Acids Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…All of the RNA samples used in this study were treated with DNase I, followed by standard Reverse Transcription using AMV RT (NEB). PCR and qRT-PCR were performed as described [ 13 , 14 ]. Real-time PCR experiment was conducted using the ABI StepOne Plus system (Life Technologies) with Absolute Blue QPCR mix (Thermal Fisher, AB-4322).…”

Section: Methodsmentioning

confidence: 99%

The Landscape and Implications of Chimeric RNAs in Cervical Cancer

Yang

Singh

et al. 2018

EBioMedicine

Self Cite

View full text Add to dashboard Cite

BackgroundGene fusions and fusion products have been proven to be ideal biomarkers and drug targets for cancer. Even though a comprehensive study of cervical cancer has been conducted as part of the Cancer Genome Atlas (TCGA) project, few recurrent gene fusions have been found, and none above 3% of frequency.MethodsWe believe that chimeric fusion RNAs generated by intergenic splicing represent a new repertoire of biomarkers and/or therapeutic targets. However, they would be missed when only genome sequences and fusions at DNA level are considered. We performed extensive data mining for chimeric RNAs using both our and TCGA cervical cancer RNA-Seq datasets. Multiple criteria were applied. We analyzed the landscape of chimeric RNAs at various levels, and from different angles.FindingsThe chimeric RNA landscape changed as different filters were applied. 15 highly frequent (>10%) chimeric RNAs were identified. LHX6-NDUFA8 was detected exclusively in cervical cancer tissues and Pap smears, but not in normal controls. Mechanistically, it is not due to interstitial deletion, but a product of cis-splicing between adjacent genes. Silencing of another recurrent chimera, SLC2A11-MIF, resulted in cell cycle arrest and reduced cellular proliferation. This effect is unique to the chimera, and not shared by the two parental genes.InterpretationHighly frequent chimeric RNAs are present in cervical cancers. They can be formed by intergenic splicing. Some have clear implications as potential biomarkers, or for shedding new light on the biology of the disease.Fund and the .

show abstract

“…Some research groups have wondered what is the role of FuTAGs in pathology, noticing the increase of readthrough transcription in stressful conditions, such as heat shock, osmotic stress [20], oxidative stress and infection [21]. It has been hypothesized that there is a correlation between FuTAGs formation and cell aging, but the lack of a strong statistical significance dismissed this hypothesis [22].…”

Section: Functions Of Futagsmentioning

confidence: 99%

“…Chwalenia et al [20] addressed the questions whether cis-SAGes are also induced under osmotic stress and whether the DoGs are correlated to the formation of cis-SAGes. They studied five cis-SAGe RNAs (CTNNBIP1-CLSTN1, DUS4L-BCAP29, CLN6-CALML, SLC29A1-HSP90AB1, UBA2-WTIP) that have DoGs from their upstream parental genes and evaluated their expression in experimental conditions of osmotic stress.…”

Section: Downstream Of Gene Containing Transcripts and Cis-sagesmentioning

confidence: 99%

“…Only at a late time after osmotic stress (24 h time point) were cis-SAGe RNAs and the corresponding DoGs positively correlated and upregulated by osmotic stress. Chwalenia et al (2017) [20] suggested that osmotic stress induces more transcriptional readthrough, with some transcripts remaining as DoGs and some processed into cis-SAGes. However, the relationship between DoGs and cis-SAGes is not clear and the functional connections between these two different phenomena require more investigations.…”

Section: Downstream Of Gene Containing Transcripts and Cis-sagesmentioning

confidence: 99%

See 1 more Smart Citation

Fusion Transcripts of Adjacent Genes: New Insights into the World of Human Complex Transcripts in Cancer

Barresi

Cosentini

Scuderi

et al. 2019

IJMS

View full text Add to dashboard Cite

The awareness of genome complexity brought a radical approach to the study of transcriptome, opening eyes to single RNAs generated from two or more adjacent genes according to the present consensus. This kind of transcript was thought to originate only from chromosomal rearrangements, but the discovery of readthrough transcription opens the doors to a new world of fusion RNAs. In the last years many possible intergenic cis-splicing mechanisms have been proposed, unveiling the origins of transcripts that contain some exons of both the upstream and downstream genes. In some cases, alternative mechanisms, such as trans-splicing and transcriptional slippage, have been proposed. Five databases, containing validated and predicted Fusion Transcripts of Adjacent Genes (FuTAGs), are available for the scientific community. A comparative analysis revealed that two of them contain the majority of the results. A complete analysis of the more widely characterized FuTAGs is provided in this review, including their expression pattern in normal tissues and in cancer. Gene structure, intergenic splicing patterns and exon junction sequences have been determined and here reported for well-characterized FuTAGs. The available functional data and the possible roles in cancer progression are discussed.

show abstract

Connections between Transcription Downstream of Genes and cis-SAGe Chimeric RNA

Cited by 6 publications

References 41 publications

A cell-based splicing reporter system to identify regulators of cis-splicing between adjacent genes

A cell-based splicing reporter system to identify regulators of cis-splicing between adjacent genes

The Landscape and Implications of Chimeric RNAs in Cervical Cancer

Fusion Transcripts of Adjacent Genes: New Insights into the World of Human Complex Transcripts in Cancer

Contact Info

Product

Resources

About