The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing

Abstract

Coupling between transcription and RNA processing is key for gene regulation. Using live-cell photobleaching techniques, we investigated the factor TCERG1, which coordinates transcriptional elongation with splicing. We demonstrate that TCERG1 is highly mobile in the nucleoplasm and that this mobility is slightly decreased when it is associated with speckles. Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) but not α-amanitin treatment reduced the mobility of TCERG1, which suggests interaction with paused transcription elongation complexes. We found that TCERG1 mobility is rapid at the transcription site (TS) of a reporter that splices post-transcriptionally and that TCERG1 is recruited to the active TS independent of the CTD of RNAPII, thus excluding phosphorylated CTD as a requirement for recruiting this factor to the TS. Importantly, the mobility of TCERG1 is reduced when the reporter splices cotranscriptionally, which suggests that TCERG1 forms new macromolecular complexes when splicing occurs cotranscriptionally. In this condition, spliceostatin A has no effect, indicating that TCERG1 rapidly binds and dissociates from stalled spliceosomal complexes and that the mobility properties of TCERG1 do not depend on events occurring after the initial spliceosome formation. Taken together, these data suggest that TCERG1 binds independently to elongation and splicing complexes, thus performing their coupling by transient interactions rather than by stable association with one or the other complexes. This finding has conceptual implications for understanding the coupling between transcription and RNA processing.

The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity

“…So, while studying such factors has enriched our knowledge of stress-response mechanisms and longevity paradigms immensely, it has not advanced discovery of the molecular distinctions between the quantitative and qualitative measures of aging. In this study, we describe a role for TCER-1, C. elegans homolog of the human transcription elongation and splicing factor, TCERG1 33,34 , in having discrete and opposite impacts on longevity and stress resilience.…”

A combinatorial view of old and new RNA polymerase II modifications

“…Interactions between the CTD of actively transcribing RNAPII and the spliceosome were thought to be mediated primarily through interactions with phosphorylated Ser5 [121]. However, the crystal structure of transcriptional elongation regulator 1 (TCERG1), which mediates interactions between RNAPII and the spliceosome, indicates that hyperphosphorylation of all three serine residues, Ser2, Ser5 and Ser7, are required for optimal interactions between RNAPII and the spliceosome during elongation [122][123][124]. Additionally, premature termination of transcription is inhibited by the interaction between the CTD phosphorylated on Ser2 and Ser5 and the human anti-termination proteins SCAF4 and SCAF8, members of the arginine/serine-rich splicing factor family [125].…”

The molecular tug of war between immunity and fertility: Emergence of conserved signaling pathways and regulatory mechanisms

“…Indeed, reduced IIS signaling inhibits the activity of several proteins essential for triggering anti‐microbial gene expression, including the conserved FOXO family members DAF‐16 in worms and dFOXO in flies. [ 94 ] But, are there dedicated transcription factor(s) that integrate these signals to directly control the immunity‐fertility crosstalk? Recent studies have revealed the existence of such “master regulator” proteins.…”

“…[ 109–111 ] Similarly, FOXO‐mediated expression of anti‐microbial proteins is conserved from worms to mammals, as is the function in lipid homeostasis. [ 94 ] The interactions between PBX, MEIS and other TALE members are also conserved across species, and while they have mostly been studied for their roles in mammalian neuronal development, there is increasing evidence for their roles in lipid homeostasis. [ 112 ] Notably, a human CEH‐60 ortholog, PBX1, has been shown to control maintenance of immune tolerance in T cells, and genetic variations in the Pbx1 gene have been associated with lupus susceptibility.…”