Unique features of transcription termination and initiation at closely spaced tandem human genes

• Published in: Molecular systems biology Vol. 18; no. 4; pp. e10682 - n/a
• Main Authors: Nissani, Noa, Ulitsky, Igor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2022; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Argonaute 2 protein; Argonaute proteins; Binding sites; Chemical synthesis; DNA-directed RNA polymerase; Elongation; EMBO09; Gene expression; Genes; genome organization; Genomes; Guanines; Humans; Interference; Mammals; Perturbation; Pol2 transcription; Promoter Regions, Genetic; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; RNA, Messenger; RNA-mediated interference; Splicing; tandem genes; Transcription elongation; Transcription initiation; Transcription termination; Transcription, Genetic; transcriptional interference; Argonaute proteins; Pol2 transcription; transcriptional interference; tandem genes; genome organization
• ISSN: 1744-4292; 1744-4292
• DOI: 10.15252/msb.202110682

The synthesis of RNA polymerase II (Pol2) products, which include messenger RNAs or long noncoding RNAs, culminates in transcription termination. How the transcriptional termination of a gene impacts the activity of promoters found immediately downstream of it, and which can be subject to potential transcriptional interference, remains largely unknown. We examined in an unbiased manner the features of the intergenic regions between pairs of ‘tandem genes’—closely spaced (< 2 kb) human genes found on the same strand. Intergenic regions separating tandem genes are enriched with guanines and are characterized by binding of several proteins, including AGO1 and AGO2 of the RNA interference pathway. Additionally, we found that Pol2 is particularly enriched in this region, and it is lost upon perturbations affecting splicing or transcriptional elongation. Perturbations of genes involved in Pol2 pausing and R loop biology preferentially affect expression of downstream genes in tandem gene pairs. Overall, we find that features associated with Pol2 pausing and accumulation rather than those associated with avoidance of transcriptional interference are the predominant driving force shaping short tandem intergenic regions. Synopsis Hundreds of human genes are transcribed in close proximity to each other and on the same strand. A systematic computational analysis reveals unique genomic features associated with intergenic regions separating these tandem genes. Co‐expression of closely spaced tandem human genes is common. Short tandem intergenic regions (STIRs) are particularly G‐rich. Several proteins, including AGO1 and AGO2, preferentially bind STIRs. Pol2 accumulates in STIRs, and perturbations related to Pol2 pausing preferentially regulate tandem gene expression. Graphical Abstract Hundreds of human genes are transcribed in close proximity to each other and on the same strand. A systematic computational analysis reveals unique genomic features associated with intergenic regions separating these tandem genes.