Transcription of genes is a fundamental property of the living. We employ biochemistry, genetics and genome wide approaches to understand how gene transcription by Pol II is controlled by the positive transcription elongation factor (P-TEFb; CDK9/CycT) and its inhibitory 7SK snRNP complex at the promoter-proximal Pol II pause release step. Moreover, we are exploring how another critical transcriptional elongation kinase, the Cdk12/CycK complex, impacts target gene expression, and how frequent CDK12 cancer mutations perturb gene transcription programs to enable cancerogenesis. Finally, through the design of novel methodologies, we are aiming to uncover mechanisms that facilitate integration of Pol II transcription with maturation of precursor RNA transcripts.