The Elongator complex catalyzes the formation of carboxymethyluridine at the "wobble base " in position 34 in tRNAs . It is involved in neurogenesis. Regulates migration and branching of projection neurons in the developing cerebral cortex through a process dependent on alpha-tubulin acetylation. May function as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB, and MAP3K14/NIK) (Waszak SM et al. 2020).
With the rapid development of cryo-electron microscopy (cryo-EM), several near-atomic structures of such higher-order transcriptional complexes of Pol II have recently been described, especially those involved in transcription initiation.
Pathogenic germline variants in established cancer predisposition genes were recently identified in 5% of patients with the malignant brain tumor medulloblastoma (Waszak SM et al. 2020).
In the medulloblastoma subgroup Sonic Hedgehog (MBSHH), rare germline variants with loss of function in ELP1 can be detected in 14% of cases. The ELP1 gene is the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% in pediatric patients with MBSHH. Most ELP1-associated medulloblastomas also had somatic alterations in PTCH1, suggesting that germline ELP1 loss-of-function variants combined with constitutive activation of the SHH pathway predispose to tumor development.