The FF4 and FF5 domains of transcription elongation regulator 1 (TCERG1) target proteins to the periphery of speckles.

Transcription elongation regulator 1 (TCERG1) is a human factor implicated in interactions with the spliceosome as a coupler of transcription and splicing. The protein is highly concentrated at the interface between speckles (the compartments enriched in splicing factors) and nearby transcription sites. Here, we identified the FF4 and FF5 domains of TCERG1 as the amino acid sequences required to direct this protein to the periphery of nuclear speckles, where coordinated transcription/RNA processing events occur. Consistent with our localization data, we observed that the FF4 and FF5 pair is required to fold in solution, thus suggesting that the pair forms a functional unit. When added to heterologous proteins, the FF4-FF5 pair is capable of targeting the resulting fusion protein to speckles. This represents, to our knowledge, the first description of a targeting signal for the localization of proteins to sites peripheral to speckled domains. Moreover, this "speckle periphery-targeting signal" contributes to the regulation of alternative splicing decisions of a reporter pre-mRNA in vivo.