1. A domain enrichment analysis of proteins involved in RNAP2 transcription regulatory machinery revealed that the TFIIS N-terminal domain (TND) is selectively enriched among transcription elongation factors.
2. A proteome-wide search uncovered several putative TND-interacting motifs (TIMs) in different transcriptional regulators, including LEDGF/HRP2, MED13/MED13L, ELL associated factors 1 and 2 (EAF1–2), PAF1 and LEO1, and two members of the SPT6 complex.
3. NMR studies revealed the structural basis for these interactions and showed that TND-TIM sequences were necessary and sufficient to induce strong and specific co-localization in the crowded nuclear environment.
The article provides a comprehensive overview of the ubiquity of TFIIS N-terminal domains (TNDs) among transcription elongation factors, as well as their potential role in mediating binary interactions with natively unstructured TND-interacting motifs (TIMs). The authors provide evidence for their claims through domain enrichment analysis, proteome-wide searches, NMR studies, live cell microscopy experiments, mass spectrometry experiments, gene expression analyses, and RNAP2 elongation dynamics experiments.
The article is generally reliable and trustworthy; however there are some points of consideration that should be noted. For example, while the authors provide evidence for their claims from a variety of sources such as NMR studies and gene expression analyses, they do not explore any possible counterarguments or alternative explanations for their findings. Additionally, while they discuss potential risks associated with disruption of a single TIM in terms of changes in gene expression and RNAP2 elongation dynamics, they do not discuss any other potential risks or implications associated with this disruption. Furthermore, while they provide evidence for their claims from a variety of sources such as NMR studies and gene expression analyses, they do not provide any evidence to support their claim that TIMs are subject to regulation by post-translational modification.
In conclusion, overall this article is reliable and trustworthy; however there are some points of consideration that should be noted regarding its lack of exploration into counterarguments or alternative explanations for its findings as well as its lack of discussion regarding potential risks associated with disruption of a single TIM.