A landscape of circular RNA expression in the human heart.

Abstract:

Aims:Circular RNA (circRNA) is a newly validated class of single-stranded RNA, ubiquitously expressed in mammalian tissues and possessing key functions including acting as microRNA sponges and as transcriptional regulators by binding to RNA-binding proteins. While independent studies confirm the expression of circRNA in various tissue types, genome-wide circRNA expression in the heart has yet to be described in detail. Methods and results:We performed deep RNA-sequencing on ribosomal-depleted RNA isolated from 12 human hearts, 25 mouse hearts and across a 28-day differentiation time-course of human embryonic stem cell-derived cardiomyocytes. Using purpose-designed bioinformatics tools, we uncovered a total of 15 318 and 3017 cardiac circRNA within human and mouse, respectively. Their abundance generally correlates with the abundance of their cognate linear RNA, but selected circRNAs exist at disproportionately higher abundance. Top highly expressed circRNA corresponded to key cardiac genes including Titin (TTN), RYR2, and DMD. The most abundant cardiac-expressed circRNA is a cytoplasmic localized single-exon circSLC8A1-1. The longest human transcript TTN alone generates up to 415 different exonic circRNA isoforms, the majority (83%) of which originates from the I-band domain. Finally, we confirmed the expression of selected cardiac circRNA by RT-PCR, Sanger sequencing and single molecule RNA-fluorescence in situ hybridization. Conclusions:Our data provide a detailed circRNA expression landscape in hearts. There is a high-abundance of specific cardiac-expressed circRNA. These findings open up a new avenue for future investigation into this emerging class of RNA.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Tan WL,Lim BT,Anene-Nzelu CG,Ackers-Johnson M,Dashi A,See K,Tiang Z,Lee DP,Chua WW,Luu TD,Li PY,Richards AM,Foo RS

doi

10.1093/cvr/cvw250

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

298-309

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvw250

journal_volume

113

pub_type

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