Figure 4.

Factors Triggering and Suppressing Premature Transcription Termination (PTT).

The molecular mechanism of PTT is unclear. However, multiple factors may trigger or prevent PTT. PTT-triggering factors include not only canonical proteins involved in RNA 3′-processing and transcription termination at gene ends [PCF11, XRN2, and the cleavage and polyadenylation (CPA) complex], but also other factors, mainly involved in RNA processing [nuclear exosome, cap-binding complex (CBC), and the Integrator complex]. Intragenic PTT is mutually exclusive with splicing; therefore, the process of splicing and splicing-promoting factors are major factors suppressing PTT. Further players preventing spurious PTT are also shown, and discussed in the main text. We note that many of the listed factors affect PTT indirectly, by affecting RNA polymerase II (Pol II) dynamics, co-transcriptional processing, or RNA stability. Further mechanistic studies are needed to provide proof of which factors have a direct role in PTT. Abbreviations: CFIm, mammalian cleavage factor I; m⁶A, modification of RNA by N6-methyladenosine.