| 1. |
- Boele, Joost, et al.
(author)
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PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease.
- 2014
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:31, s. 11467-11472
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Journal article (peer-reviewed)abstract
- Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt at their 3' end, and moreover that the 3' end of miR-21 is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting that PAPD5-mediated adenylation of miR-21 leads to its degradation. Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested that PARN degrades miR-21 in the 3'-to-5' direction. In accordance with this model, microarray expression profiling demonstrated that PAPD5 knockdown results in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and trimming process, and that this pathway is disrupted in cancer and other proliferative diseases.
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| 2. |
- Brueffer, Christian, et al.
(author)
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Biopython Project Update 2016
- 2016
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Conference paper (other academic/artistic)abstract
- The Biopython Project is a long-running distributed collaborative effort, supported by the Open Bioinformatics Foundation, which develops a freely available Python library for biological computation.We present here details of the latest Biopython release - version 1.66. New features include: extended Bio.KEGG and Bio.Graphics modules to support drawing KEGG pathways with transparency; extended “abi” Bio.SeqIO parser to decode almost all documented fields used by ABIF instruments; a QCPSuperimposer module using the Quaternion Characteristic Polynomial algorithm for superimposing structures to Bio.PDB; and an extended Bio.Entrez module to implement the NCBI Entrez Citation Matching function and to support NCBI XML files with XSD schemas. Additionally we fixed miscellaneous bugs, enhanced our test suite and continued our efforts to abide by the PEP8 coding style guidelines.We are currently preparing a new release – version 1.67 – that will deprecate the ability to compare SeqRecord objects with “==”, which sometimes lead to surprising results. In addition it will feature a new experimental Bio.phenotype module for working with Phenotype Microarray data; updates to Bio.Data toinclude NCBI genetic code table 25, covering Candidate Division SR1 and Gracilibacteria; an update to Bio.Restriction to include the REBASE May 2016 restriction enzyme list; updates to BioSQL to use foreign keys with SQLite3 databases; as well as corrections to the Bio.Entrez module and the MMCIF structure parser.Our website has been migrated from MediaWiki to GitHub Pages and is now under version control. The continuous integration process on GitHub has been enhanced by including external services like Landscape, Quantified Code and Codecov to perform quality review, test coverage analysis and generation of quality metrics.Finally, our range of Docker containers has been greatly enhanced. In addition to a basic container that includes Python 2 and 3 with Biopython and all its dependencies, as well as a BioSQL container, we now also provide two versions of Jupyter notebook containers: a basic one, and a version including the Biopython tutorial as notebooks.
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| 3. |
- Newie, Inga, et al.
(author)
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HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- We previously reported that the human HER2 gene encodes the intronic microRNA mir-4728, which is overexpressed together with its oncogenic host gene and may act independently of the HER2 receptor. More recently, we also reported that the oncogenic miR-21-5p is regulated by 3′ tailing and trimming by the non-canonical poly(A) polymerase PAPD5 and the ribonuclease PARN. Here we demonstrate a dual function for the HER2 locus in upregulation of miR-21-5p; while HER2 signalling activates transcription of mir-21, miR-4728-3p specifically stabilises miR-21-5p through inhibition of PAPD5. Our results establish a new and unexpected oncogenic role for the HER2 locus that is not currently being targeted by any anti-HER2 therapy.
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