A comprehensive profile of circulating RNAs in human serum

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ABSTRACT

Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA). We also investigated biological and technical variation in expression, and the results suggest that many RNA molecules identified in serum contain signs of biological variation. They are therefore unlikely to be random degradation by-products. In addition, the presence of specific fragments of tRNA, snoRNA, Vault RNA and Y_RNA indicates protection from degradation. Our results suggest that many circulating RNAs in serum can be potential biomarkers.

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A germline-specific class of small RNAs binds mammalian Piwi proteins.

Angélique Girard, Ravi Sachidanandam, Gregory Hannon … (2006)

Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21-22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of approximately 29-30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis.

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Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells.

Ryan Morin, Michael D O'Connor, Malachi Griffith … (2008)

MicroRNAs (miRNAs) are emerging as important, albeit poorly characterized, regulators of biological processes. Key to further elucidation of their roles is the generation of more complete lists of their numbers and expression changes in different cell states. Here, we report a new method for surveying the expression of small RNAs, including microRNAs, using Illumina sequencing technology. We also present a set of methods for annotating sequences deriving from known miRNAs, identifying variability in mature miRNA sequences, and identifying sequences belonging to previously unidentified miRNA genes. Application of this approach to RNA from human embryonic stem cells obtained before and after their differentiation into embryoid bodies revealed the sequences and expression levels of 334 known plus 104 novel miRNA genes. One hundred seventy-one known and 23 novel microRNA sequences exhibited significant expression differences between these two developmental states. Owing to the increased number of sequence reads, these libraries represent the deepest miRNA sampling to date, spanning nearly six orders of magnitude of expression. The predicted targets of those miRNAs enriched in either sample shared common features. Included among the high-ranked predicted gene targets are those implicated in differentiation, cell cycle control, programmed cell death, and transcriptional regulation.

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Data quality at the Cancer Registry of Norway: an overview of comparability, completeness, validity and timeliness.

Inger Kristin Larsen, Milada C Småstuen, Tom Borge Johannesen … (2009)

To provide a comprehensive evaluation of the quality of the data collected on both solid and non-solid tumours at the Cancer Registry of Norway (CRN). Established quantitative and semi-quantitative methods were used to assess comparability, completeness, accuracy and timeliness of data for the period 1953-2005, with special attention to the registration period 2001-2005. The CRN coding and classification system by and large follows international standards, with some further subdivisions of morphology groupings performed in-house. The overall completeness was estimated at 98.8% for the registration period 2001-2005. There remains a variable degree of under-reporting particularly for haematological malignancies (C90-95) and tumours of the central nervous system (C70-72). For the same period, 93.8% of the cases were morphologically verified (site-specific range: 60.0-99.8%). The under-reporting in 2005 due to timely publication is estimated at 2.2% overall, based on the number of cases received at the registry during the following year. This review suggests the routines in place at the CRN yields comparable data that can be considered reasonably accurate, close-to-complete and timely, thereby justifying our policy of the reporting of annual incidence one year after the year of diagnosis.

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Author and article information

Journal

Journal ID (nlm-ta): RNA Biol

Journal ID (iso-abbrev): RNA Biol

Journal ID (publisher-id): KRNB

Journal ID (publisher-id): krnb20

Title: RNA Biology

Publisher: Taylor & Francis

ISSN (Print): 1547-6286

ISSN (Electronic): 1555-8584

Publication date Collection: 2018

Publication date (Electronic): 8 December 2017

Publication date PMC-release: 8 December 2017

Volume: 15

Issue: 2

Pages: 242-250

Affiliations

[a ]Department of Research, Cancer Registry of Norway , Oslo, Norway

[b ]Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital , Nydalen, Oslo, Norway

[c ]Department of Clinical Bioinformatics, Saarland University , Saarbruecken, Germany

[d ]Department of Human Genetics, Saarland University , Homburg/Saar, Germany

[e ]Department of Medical Genetics, Oslo University Hospital and University of Oslo , Oslo, Norway

[f ]PharmaTox Strategic Research Initiative, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo , Oslo, Norway

Author notes

CONTACT Sinan Uğur Umu sinan.ugur.umu@ 123456kreftregisteret.no Kreftregisteret (Cancer Registry of Norway) , Postboks 5313, Majorstuen, Oslo 0304, Norway

Supplemental data for this article can be accessed on the publisher's website.

Author information

Sinan Uğur Umu http://orcid.org/0000-0001-8081-7819

Hilde Langseth http://orcid.org/0000-0002-9446-4855

Cecilie Bucher-Johannessen http://orcid.org/0000-0003-3277-269X

Bastian Fromm https://orcid.org/0000-0003-0352-3037

Marianne Lauritzen https://orcid.org/0000-0002-0761-2558

Magnus Leithaug https://orcid.org/0000-0002-0271-0677

Trine B. Rounge http://orcid.org/0000-0003-2677-2722

Article

Publisher ID: 1403003

DOI: 10.1080/15476286.2017.1403003

PMC ID: 5798962

PubMed ID: 29219730

SO-VID: 904ff6ba-f9df-4768-b76a-ac606906c0ee

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

History

Date received : 19 September 2017

Date revision received : 30 October 2017

Date accepted : 30 October 2017

Page count

Figures: 4, Tables: 1, Equations: 0, References: 84, Pages: 9

Funding

Funded by: Norges Forskningsråd 10.13039/501100005416

Award ID: 248791/H10

Funded by: Norges Forskningsråd 10.13039/501100005416

Award ID: 229621/H10

The study was funded by the Research Council of Norway under the Program Human Biobanks and Health Data (grant numbers 229621/H10 and 248791/H10). BF was supported by the South-Eastern Norway Regional Health Authority, project number: 229621.

A comprehensive profile of circulating RNAs in human serum

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Most cited references 48

A germline-specific class of small RNAs binds mammalian Piwi proteins.

Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells.

Data quality at the Cancer Registry of Norway: an overview of comparability, completeness, validity and timeliness.

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