Terminating the transcript: breaking up is hard to do

Transcription termination occurs when a transcribing RNA polymerase releases the DNA template and the nascent RNA. Termination is required for preventing the inappropriate transcription of downstream genes, and for recycling of the polymerase. Recent studies in yeast point to the existence of gene loops, in which a transcriptionally active gene’s termination region can be physically linked to its promoter site; in this situation, termination can additionally serve to facilitate transcriptional reinitiation (O’Sullivan et al. 2004; Ansari and Hampsey 2005). Termination by prokaryotic RNA polymerases, as well as eukaryotic RNA polymerase (Pol) I and Pol III, occurs at specific positions, requiring DNA or RNA cis elements that can directly or indirectly destabilize the elongating polymerase–DNA–RNA ternary complex (for reviews, see Henkin 2000; Paule and White 2000). However, for protein-encoding genes, transcribed exclusively by Pol II, transcription in most cases terminates stochastically, independently of simple cis signals, and frequently 500 or more base pairs (bp) downstream of the poly(A) signal. This unique and complex mode of termination by Pol II may have arisen to allow for transcription of very long genes without prematurely stopping at terminator-like sequences that occur by chance throughout the gene. Studies in the area of Pol II termination have sparked some debate, as two models, each supported by many studies, have emerged to explain what provokes Pol II to release the template (Fig. 1). A new study by Luo et al. (2006) presents evidence, however, that aspects of both models can be linked together and leads to new, integrated models of transcription termination.