uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
U1-like snRNAs lacking complementarity to canonical 5' splice sites
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.ORCID iD: 0000-0002-4383-9880
Show others and affiliations
2006 (English)In: RNA: A publication of the RNA Society, ISSN 1355-8382, E-ISSN 1469-9001, Vol. 12, no 9, 1603-1611 p.Article in journal (Refereed) Published
Abstract [en]

We have detected a surprising heterogeneity among human spliceosomal U1 small nuclear RNA (snRNA). Most interestingly, we have identified three U1 snRNA variants that lack complementarity to the canonical 5' splice site (5'SS) GU dinucleotide. Furthermore, we have observed heterogeneity among the identified variant U1 snRNA genes caused by single nucleotide polymorphism (SNP). The identified snRNAs were ubiquitously expressed in a variety of human tissues representing different stages of development and displayed features of functional spliceosomal snRNAs, i.e., trimethylated cap structures, association with Sm proteins and presence in nuclear RNA-protein complexes. The unanticipated heterogeneity among spliceosomal snRNAs could contribute to the complexity of vertebrates by expanding the coding capacity of their genomes.

Place, publisher, year, edition, pages
2006. Vol. 12, no 9, 1603-1611 p.
Keyword [en]
U1 snRNP, mRNA splicing, noncanonical 5 ' splice site, SNP, genome complexity
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97962DOI: 10.1261/rna.26506ISI: 000240145400001PubMedID: 16829670OAI: oai:DiVA.org:uu-97962DiVA: diva2:173093
Available from: 2009-01-01 Created: 2009-01-01 Last updated: 2016-09-09Bibliographically approved
In thesis
1. Computational Approaches to the Identification and Characterization of Non-Coding RNA Genes
Open this publication in new window or tab >>Computational Approaches to the Identification and Characterization of Non-Coding RNA Genes
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Non-coding RNAs (ncRNAs) have emerged as highly diverse and powerful key players in the cell, the range of capabilities spanning from catalyzing essential processes in all living organisms, e.g. protein synthesis, to being highly specific regulators of gene expression. To fully understand the functional significance of ncRNAs, it is of critical importance to identify and characterize the repertoire of ncRNAs in the cell. Practically every genome-wide screen to identify ncRNAs has revealed large numbers of expressed ncRNAs and often identified species-specific ncRNA families of unknown function. Recent years' advancement in high-throughput sequencing techniques necessitates efficient and reliable methods for computational identification and annotation of genes. A major aim in the work underlying this thesis has been to develop and use computational tools for the identification and characterization of ncRNA genes.

We used computational approaches in combination with experimental methods to study the ncRNA repertoire of the model organism Dictyostelium discoideum. We report ncRNA genes belonging to well-characterized gene families as well as previously unknown and potentially species-specific ncRNA families. The complicated task of de novo ncRNA gene prediction was successfully addressed by developing a method for nucleotide composition-based gene prediction using maximal-scoring partial sums and considering overlapping dinucleotides.

We also report a substantial heterogeneity among human spliceosomal snRNAs. Northern blot analysis and cDNA cloning, as well as bioinformatical analysis of publicly available microarray data, revealed a large number of expressed snRNAs. In particular, U1 snRNA variants with several nucleotide substitutions that could potentially have dramatic effects on splice site recognition were identified.

In conclusion, we have by using computational approaches combined with experimental analysis identified a rich and diverse ncRNA repertoire in the eukaryotes D. discoideum and Homo sapiens. The surprising diversity among the snRNAs in H. sapiens suggests a functional involvement in recognition of non-canonical introns and regulation of messenger RNA splicing.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 589
Keyword
ncRNA, snRNA, U1, splice site, alternative splicing, Dictyostelium, nucleotide composition, partial sums
National Category
Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:uu:diva-9518 (URN)978-91-554-7386-0 (ISBN)
Public defence
2009-01-30, B21, Biomedicinskt Centrum, Husargatan 3, Uppsala, 10:00
Opponent
Supervisors
Available from: 2009-01-01 Created: 2009-01-01Bibliographically approved
2. Understanding the Noise: Spliceosomal snRNA Profiling
Open this publication in new window or tab >>Understanding the Noise: Spliceosomal snRNA Profiling
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The concept of the gene has been constantly challenged by new discoveries in the life sciences. Recent challenging observations include the high frequency of alternative splicing events and the common transcription of non-protein-coding-RNAs (ncRNAs) from the genome. The latter has long been considered noise in biological systems. Multiple lines of evidence from genomic studies indicate that alternative splicing and ncRNA play important roles in expanding proteome diversity in eukaryotes. Here, the aim is to find the link between alternative splicing and ncRNAs by studying the expression profile of the spliceosomal snRNAs (U snRNA).

Spliceosomal snRNAs are essential for pre-mRNA splicing in eukaryotes. They participate in splice site selection, recruitment of protein factors and catalyzing the splicing reaction. Because of this, both the abundance and diversity of U snRNAs were expected to be large. In our study we deeply analyzed the U snRNA population in primates using a combination of bioinformatical, biochemical and high throughput sequencing approaches. This transcriptome profiling has revealed that human, chimpanzee and rhesus have similar U snRNA populations, i.e. the vast majority of U snRNAs originate from few well-defined gene loci and the heterogeneity observed in U snRNA populations was largely due to the presence of SNPs at these loci. It seems that the gene loci that could potentially encode a significantly heterogeneous population of U snRNAs are mostly silent. Only few minority transcripts were detected in our study, and among them three U1-like snRNAs might play a role in the regulation of alternative splicing by recognizing non-canonical splicing sites.

Mutations of U snRNA have been shown to impact the splicing process. Therefore, our study provides a reference to study the biological significance of SNPs in U snRNA genes and their association with diseases.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 45 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 924
Keyword
ncRNA, snRNA, U1, splice site, alternative splicing, high-throughput sequencing, 454, SNP
National Category
Natural Sciences Biochemistry and Molecular Biology
Research subject
Molecular Cellbiology
Identifiers
urn:nbn:se:uu:diva-172403 (URN)978-91-554-8341-8 (ISBN)
Public defence
2012-05-24, B41, Husargatan 3, Biomedicinskt Centrum, Uppsala University, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2012-05-02 Created: 2012-04-10 Last updated: 2012-08-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Schuster, Jens

Search in DiVA

By author/editor
Schuster, Jens
By organisation
Department of Cell and Molecular Biology
In the same journal
RNA: A publication of the RNA Society
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 510 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf