MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation

The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and is expressed in a strictly growth factor-dependent manner in non-tumor cells. Here we show that MYC directly binds SPT5, a subunit of the RNA polymerase II (POL2) elongation factor DSIF. MYC recruits SPT5 to genes and enables the CDK7-dependent transfer of SPT5 onto POL2. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. In addition, MYC increases the directionality of promoters by stimulating sense transcription and suppressing the synthesis of antisense RNAs. Our results argue that MYC controls the productive assembly of POL2 with general elongation factors to form processive elongation complexes. The high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, slows transcription at growth-suppressive genes and promotes uncontrolled cellular growth. 4sUDRB Seq, 4sU Seq, ChIPSeq (SPT5,Total Pol2 & Ser2 Pol2) in various levels of MYC or SPT5