Genome-wide characterization of human L1 antisense promoter-driven transcripts.
Long INterspersed Element-1 (LINE-1 or L1) is the only autonomously active, transposable element in the human genome. L1 sequences comprise approximately 17 % of the human genome, but only the evolutionarily recent, human-specific subfamily is retrotransposition competent. The L1 promoter has a bidirectional orientation containing a sense promoter that drives the transcription of two proteins required for retrotransposition and an antisense promoter. The L1 antisense promoter can drive transcription of chimeric transcripts: 5' L1 antisense sequences spliced to the exons of neighboring genes.



The impact of L1 antisense promoter activity on cellular transcriptomes is poorly understood. To investigate this, we analyzed GenBank ESTs for messenger RNAs that initiate in the L1 antisense promoter. We identified 988 putative L1 antisense chimeric transcripts, 911 of which have not been previously reported. These appear to be alternative genic transcripts, sense-oriented with respect to gene and initiating near, but typically downstream of, the gene transcriptional start site. In multiple cell lines, L1 antisense promoters display enrichment for YY1 transcription factor and histone modifications associated with active promoters. Global run-on sequencing data support the activity of the L1 antisense promoter. We independently detected 124 L1 antisense chimeric transcripts using long read Pacific Biosciences RNA-seq data. Furthermore, we validated four chimeric transcripts by quantitative RT-PCR and Sanger sequencing and demonstrated that they are readily detectable in many normal human tissues.



We present a comprehensive characterization of human L1 antisense promoter-driven transcripts and provide substantial evidence that they are transcribed in a variety of human cell-types. Our findings reveal a new wide-reaching aspect of L1 biology by identifying antisense transcripts affecting as many as 4 % of all human genes.
Department of Molecular Biology, Cell Biology, and Biochemistry, Center for Computational Molecular Biology, Brown University, Providence, RI, 02912, USA.
Steven W
SW
Criscione
Department of Pathology, Yale University, New Haven, CT, 06510, USA.|Department of Dermatology, Division of Dermatopathology, Yale University, New Haven, CT, 06510, USA.
Nicholas
N
Theodosakis
Department of Pathology, Yale University, New Haven, CT, 06510, USA.|Department of Dermatology, Division of Dermatopathology, Yale University, New Haven, CT, 06510, USA.
Goran
G
Micevic
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Toby C
TC
Cornish
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|High Throughput (HiT) Biology Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kathleen H
KH
Burns
Department of Molecular Biology, Cell Biology, and Biochemistry, Center for Computational Molecular Biology, Brown University, Providence, RI, 02912, USA. Nicola_Neretti@brown.edu.
Nicola
N
Neretti
Department of Pathology, Yale University, New Haven, CT, 06510, USA. Nemanja.Rodic@Yale.edu.|Department of Dermatology, Division of Dermatopathology, Yale University, New Haven, CT, 06510, USA. Nemanja.Rodic@Yale.edu.
Nemanja
N
Rodić
D000818:Animals; D020224:Expressed Sequence Tags; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D051379:Mice; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense; D018626:Retroelements; D014158:Transcription, Genetic
D016372:RNA, Antisense; D018626:Retroelements
Antisense promoter; Chimeric transcript; EST; L1; LINE-1; PacBio; Retrotransposon; Transposon; YY1