Abstract
In this study, we introduced a general framework to use PacBio full-length transcriptome sequencing for the investigation of the fundamental problems in mitochondrial biology, e.g. genome arrangement, heteroplasmy, RNA processing and the regulation of transcription or replication. As a result, we produced the first full-length human mitochondrial transcriptome from the MCF7 cell line based on the PacBio platform and characterized the human mitochondrial transcriptome with more comprehensive and accurate information. The most important finding is two novel genes hsa-MDL1 and hsa-MDL1AS, which are encoded by the mitochondrial D-loop regions. We propose hsa-MDL1 and hsa-MDL1AS, as the precursors of transcription initiation RNAs (tiRNAs), belong to a novel class of long non-coding RNAs (lnRNAs), which is named as long tiRNAs (ltiRNAs). Based on the mitochondrial RNA processing model, the primary tiRNAs, precursors and mature tiRNAs could be discovered to completely reveal tiRNAs from their origins to functions. The ltiRNA/tiRNA system and their regulation mechanisms could exist ubiquitously in eukaryotes and prokaryotes. These findings will enrich the basic concepts in the field of mitochondrial biology, lnRNA functions and regulation of gene expression.
Abbreviations
- tiRNA
- transcription initiation RNA
- ltiRNA
- long tiRNA
- lncRNA
- long non-coding RNA
- mtDNA
- mitochondrial DNA
- D-loop
- Displacement-loop
- ATP
- Adenosine Triphosphate
- NGS
- Next Generation Sequencing
- SMRT
- Single-molecule Real-time
- CCS
- Circular Consensus Sequencing
- H-strand
- Heavy strand
- L-strand
- Light strand
- LCB
- Locally Collinear Block
- OH
- the origin of H-strand replication
- OL
- the origin of L-strand replication
- ITH1
- the initiation of the first transcription site on H-strand
- ITH2
- the initiation of the second transcription site on H-strand
- ITL
- the initiation of transcription site on L-strand
- SNP
- Single Nucleotide Polymorphism
- eft
- Erthesina fullo Thunberg
- HCC
- Hepatocellular Carcinoma
- TIS
- Transcription Initiation Site