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Transposable B2 SINE elements can provide mobile RNA polymerase II promoters

Abstract

Short interspersed elements (SINEs) are highly abundant components of mammalian genomes that are propagated by retrotransposition. SINEs are recognized as a causal agent of human disease and must also have had a profound influence in shaping eukaryotic genomes1. The B2 SINE family constitutes approximately 0.7% of total mouse genomic DNA (ref. 2) and is also found at low abundance in humans3. It resembles the Alu family in several respects, such as its mechanism of propagation. B2 SINEs are derived from tRNA and are transcribed by RNA polymerase (pol) III to generate short transcripts that are not translated4,5. We find here, however, that one B2 SINE also carries an active pol II promoter located outside the tRNA region. Indeed, a B2 element is responsible for the production of a mouse Lama3 transcript. The B2 pol II promoters can be bound and stimulated by the transcription factor USF (for upstream stimulatory factor), as shown by transient transfection experiments. Moreover, this pol II activity does not preclude the pol III transcription necessary for retrotransposition6. Dispersal of B2 SINEs by retrotransposition may therefore have provided numerous opportunities for creating regulated pol II transcription at novel genomic sites. This mechanism may have allowed the evolution of new transcription units and new genes.

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Figure 1: Identification of a pol II promoter in a B2 SINE.
Figure 2: Characterization of the minimal pol II promoter of the Lama3 B2 SINE.
Figure 3: B2 initiator sequences can be bound and activated by USF.
Figure 4: The Lama3 B2 SINE contains a functional internal pol III promoter.
Figure 5: Sequence alignment of the initiator and TATA box regions of the B2 (I) consensus4,5 with several Mus musculus pol II promoters from the Eukaryotic Promoter Database, for which the transcription start site has been determined experimentally (http://www.epd.isb-sib.ch/; SIECR, Lausanne).

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Acknowledgements

We thank J.M. Egly and F. Coin for pol II transcription factors and HeLa whole cell extract; P. Pognonec for pRK-USF1 and pET-USF; G. Pages for pVEGF; and P. Rigby for critical reading of the manuscript. This work was supported by grants from INSERM, Association pour la Recherche sur le Cancer (contract 9657) and EEC BIOMED 2 (BMH4-97-2062).

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Correspondence to Daniel Aberdam.

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Ferrigno, O., Virolle, T., Djabari, Z. et al. Transposable B2 SINE elements can provide mobile RNA polymerase II promoters. Nat Genet 28, 77–81 (2001). https://doi.org/10.1038/ng0501-77

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