The histone methyltransferase NSD3 enhances rDNA transcription in cancer

Most studies have focused on the short isoform of NSD3, lacking enzymatic activity while very little is known on the long NSD3 isoform, NSD3L, which also includes the SET methyltransferase domain. We found that NSD3L is a key regulator of ribosome biogenesis in cancer.

NSD3L localises in the nucleolus and interacts with several nucleolar proteins. NSD3L overexpression is associated with enhanced expression of nucleolar genes and ribosomal RNA (rRNA) transcription in several tumour types. In cancer cells, but not in immortalised fibroblasts, NSD3L knock-down abrogates rRNA transcription and the binding to the entire sequence of ribosomal DNA of Polymerase I, as well as of the PolI activator upstream binding factor UBF, both required for rRNA transcription.