Are gene loops the cause of transcriptional noise?

• Many genes produce mRNA irregularly, resulting in infrequent transcription bursts.
• Transcriptional bursting is a major source of noise, but its cause is unknown.
• Gene loops are a possible mechanism for generating bursts.
• Links between noise, transcription, looping, and polymerase pausing are examined.

Expression levels of the same mRNA or protein vary significantly among the cells of an otherwise identical population. Such biological noise has great functional implications and is largely due to transcriptional bursting, the episodic production of mRNAs in short, intense bursts, interspersed by periods of transcriptional inactivity. Bursting has been demonstrated in a wide range of pro- and eukaryotic species, attesting to its universal importance. However, the mechanistic origins of bursting remain elusive. A different type of phenomenon, which has also been suggested to be widespread, is the physical interaction between the promoter and 3′ end of a gene. Several functional roles have been proposed for such gene loops, including the facilitation of transcriptional reinitiation. Here, I discuss the most recent findings related to these subjects and argue that gene loops are a likely cause of transcriptional bursting and, thus, biological noise.