@article {VlamingHanneke2022Stot,
	title = {Screening thousands of transcribed coding and non-coding regions reveals sequence determinants of RNA polymerase II elongation potential},
	journal = {Nature structural \& molecular biology},
	volume = {29},
	number = {6},
	year = {2022},
	pages = {613{\textendash}620},
	publisher = {Nature Publishing Group},
	address = {United States},
	abstract = {Precise regulation of transcription by RNA polymerase II (RNAPII) is critical for organismal growth and development. However, what determines whether an engaged RNAPII will synthesize a full-length transcript or terminate prematurely is poorly understood. Notably, RNAPII is far more susceptible to termination when transcribing non-coding RNAs than when synthesizing protein-coding mRNAs, but the mechanisms underlying this are unclear. To investigate the impact of transcribed sequence on elongation potential, we developed a method to screen the effects of thousands of INtegrated Sequences on Expression of RNA and Translation using high-throughput sequencing (INSERT-seq). We found that higher AT content in non-coding RNAs, rather than specific sequence motifs, drives RNAPII termination. Further, we demonstrate that 5{\textquoteright} splice sites autonomously stimulate processive transcription, even in the absence of polyadenylation signals. Our results reveal a potent role for the transcribed sequence in dictating gene output and demonstrate the power of INSERT-seq toward illuminating these contributions.},
	keywords = {DNA-directed RNA polymerase, Elongation, Gene Expression, Gene regulation, Gene sequencing, Next-generation sequencing, Non-coding RNA, Nucleotide sequence, Polyadenylation, Ribonucleic acid, RNA, RNA polymerase, RNA Polymerase II, Signal Processing, synthesis, Transcription},
	issn = {1545-9993},
	url = {https://www.nature.com/articles/s41594-022-00785-9},
	author = {Vlaming, Hanneke and Mimoso, Claudia A and Field, Andrew R and Martin, Benjamin J E and Adelman, Karen}
}
