| TH1L (also known as NELF‑C/D) is a metazoan‑specific subunit of the Negative Elongation Factor (NELF) complex, which also includes WHSC2 (NELF‑A), COBRA‑1 (NELF‑B), and NELF‑E and is broadly expressed in mammalian tissues involved in regulated transcription. TH1L, together with COBRA‑1, serves as an integral structural core of the NELF complex that physically links WHSC2 and NELF‑E, enabling assembly of a functional tetrameric NELF complex capable of associating with RNA Polymerase II (RNAPII). The NELF complex cooperates with the DRB‑sensitivity‑inducing factor (DSIF) complex at the promoter‑proximal region of many genes to inhibit RNAPII elongation and establish a paused state, in which the polymerase is halted near the transcription start site and requires additional signaling for productive elongation. Release of RNAPII from this pause is mediated by the positive transcription elongation factor b (p‑TEFb), which phosphorylates NELF (including NELF‑E) and the carboxy‑terminal domain (CTD) of the largest RNAPII subunit, thereby weakening the NELF–RNAPII association and permitting elongation to proceed. Within the NELF complex, TH1L contributes to proper subunit organization and complex stability, and alternative translation initiation at the TH1L locus generates distinct isoforms that may influence complex stoichiometry or localization. TH1L‑containing NELF‑C and NELF‑D isoforms can both support NELF assembly and function, linking TH1L to the regulation of a broad transcriptional program that controls immediate‑early genes, developmental regulators, and stress‑response loci. |
Lane 1: HCT116, Lane 2: RAW264.7, Lane 3: COS-7
