Search

Abstract Current single-cell RNA-seq approaches are hindered by preamplification bias, loss of strand of origin information, and the inability to observe small-RNA and mRNA dual transcriptomes. Here, we introduce a single-cell holo-transcriptome sequencing (Holo-Seq) that overcomes all three hurdles. Holo-Seq has the same quantitative accuracy and uniform coverage with a complete strand of origin information as bulk RNA-seq. Most importantly, Holo-Seq can simultaneously observe small RNAs and mRNAs in a single cell. Furthermore, we acquire small RNA and mRNA dual transcriptomes of 32 human hepatocellular carcinoma single cells, which display the genome-wide super-enhancer activity and hepatic neoplasm kinetics of these cells.

Microsomal triglyceride transfer protein (MTTP) is essential for the assembly and secretion of apoB-containing lipoproteins. Here, we report the presence of genes on the anti-sense strands of the human MTTP and mouse Mttp genes. The gene on the anti-sense strand of the human MTTP gene is called MTTP-AS1. It consists of 5 exons and 4 introns and codes for two different transcripts MTTP-AS1-Long and MTTP-AS1-Short. Exons 3 and 5 of the MTTP-AS1 gene are ancient and evolutionary conserved whereas exons 2 and 4 are primate specific. MTTP-AS1-Long is mainly in the liver and is in the cytoplasm of human hepatoma cells. MTTP-AS1-Short is in the testis. The MTTP-AS1-Long transcript shows complementarity with two different exons of the MTTP transcript. The gene on the opposite strand of the mouse Mttp gene is named as Mttpos. It consists of 2 exons and one intron and codes for one transcript. Partial sequence of the Mttpos exon 2 is homologous in several species from rodents to primates. Mttpos transcript is present in mouse liver, small intestine and testis. The Mttpos transcript shows significant complementarity with the corresponding mouse Mttp mRNA sequences. Further, we identified a conserved sequence in the human MTTP-AS1-Long and mouse Mttpos transcripts indicating for possible evolutionarily conserved regulatory function for these long noncoding RNAs. It is likely that these newly identified long noncoding RNAs interact with their complementary sequences in MTTP mRNAs and affect their stability or translation. • The anti-sense strand of the human MTTP gene transcribes two noncoding RNAs. • The MTTP-AS1-Long noncoding RNA is in the cytosol. • The anti-sense strand of the mouse Mttp gene contains one noncoding RNA. [ABSTRACT FROM AUTHOR]

Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte antigens HLA-B54 in Japan and China and HLA-A11 in Korea suggest that the susceptible locus for DPB is located between the HLA-B and HLA-A genes. We have previously reported that the susceptibility gene for DPB could be localized within a 200-kb segment between the S and TFIIH loci in the HLA class I region, using refined microsatellite-based association mapping. However, no genes have been recognized in this candidate region to date. In order to identify a novel candidate gene for DPB from this segment, the expressed sequence tag databases were searched using the genomic sequence. As a result, a cDNA clone was isolated from a human lung cDNA library. This gene, designated C6orf37 (Chromosome 6 open reading frame 37), spans approximately 2.5 kb and consists of two exons encoding a 235-amino acid protein, sharing homology with the mucin-like domain of human zonadhesin, which is a sperm multiple-domain transmembrane protein with the sperm zona pellucida binding activity. Unexpectedly, RT-PCR analysis detected transcripts from the anti-sense DNA strand of this C6orf37 locus. The gene designated as C6orf37OS (C6orf37 Opposite Strand) and represented by these anti-sense transcripts contained no open reading frame. The transcripts from C6orf37 and C6orf37OS were observed in numerous tissues, with most-abundant expression in lung, kidney, and testis. Taken together, these results, especially the abundant expression in lung, indicate that C6orf37 and C6orf37OS are excellent candidate genes for DPB. [ABSTRACT FROM AUTHOR]