Biallelic BRF2 mutations cause syndromic immunodeficiency and change RNA polymerase III-mediated transcription

TFIIB-related factor 2 (BRF2) crucially recruits RNA polymerase III (Pol III) to type III promoters containing a TATA box. These promoters encompass crucial components such as U6 spliceosomal RNA, tRNA processing enzyme RNase P, and selenocysteine tRNA. The results on cancer occurrence due to overexpression of BRF2 are known, but genetic disorders caused by mutations in BRF2 are still not well understood. Here, we first identified biallelic BRF2 variants exhibiting defective RNA Pol III activity to type III promoter in a familial patient presenting multiple anomalous features and primary immunodeficiency. Depletion of BRF2 was carried out by small interfering RNAs (siRNAs) against human BRF2 (siRNA ID: 55290) and a negative control.