Full-length mRNA sequencing uncovers a widespread coupling between transcription initiation and mRNA processing.

Genome Biol 2018 03 29;19(1):46. Epub 2018 Mar 29.

Department of Human Genetics, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.

Background: The multifaceted control of gene expression requires tight coordination of regulatory mechanisms at transcriptional and post-transcriptional level. Here, we studied the interdependence of transcription initiation, splicing and polyadenylation events on single mRNA molecules by full-length mRNA sequencing.

Results: In MCF-7 breast cancer cells, we find 2700 genes with interdependent alternative transcription initiation, splicing and polyadenylation events, both in proximal and distant parts of mRNA molecules, including examples of coupling between transcription start sites and polyadenylation sites. The analysis of three human primary tissues (brain, heart and liver) reveals similar patterns of interdependency between transcription initiation and mRNA processing events. We predict thousands of novel open reading frames from full-length mRNA sequences and obtained evidence for their translation by shotgun proteomics. The mapping database rescues 358 previously unassigned peptides and improves the assignment of others. By recognizing sample-specific amino-acid changes and novel splicing patterns, full-length mRNA sequencing improves proteogenomics analysis of MCF-7 cells.

Conclusions: Our findings demonstrate that our understanding of transcriptome complexity is far from complete and provides a basis to reveal largely unresolved mechanisms that coordinate transcription initiation and mRNA processing.

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-018-1418-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877393PMC
March 2018
28 Reads

Publication Analysis

Top Keywords

transcription initiation
20
full-length mrna
16
initiation mrna
12
mrna processing
12
coupling transcription
8
mrna
8
splicing polyadenylation
8
polyadenylation events
8
mrna molecules
8
mrna sequencing
8
initiation splicing
8
transcription
6
initiation
5
liver reveals
4
processing events
4
patterns interdependency
4
events predict
4
interdependency transcription
4
reveals patterns
4
heart liver
4

Altmetric Statistics

References

(Supplied by CrossRef)

Q Pan et al.
Nat Genet. 2008

Y Barash et al.
Nature. 2010

ET Wang et al.
Nature. 2008

D Auboeuf et al.
Mol Cell Biol. 2005

DL Bentley et al.
Nat Rev Genet. 2014

H Tilgner et al.
G3 (Bethesda) 2013

S Koren et al.
Nat Biotechnol. 2012

H Tilgner et al.
Proc Natl Acad Sci U S A. 2014

D Sharon et al.
Nat Biotechnol. 2013

KF Au et al.
Proc Natl Acad Sci U S A. 2013

Similar Publications