Proteomics

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Comprehensive peptide analysis of mouse brain striatum identifies novel sORF-encoded polypeptides


ABSTRACT: Bio-active peptides are involved in the regulation of most if not all physiological processes in the body. Classical bio-active peptides (CBAPs) are mostly cleaved from a larger precursor protein and stored in secretion vesicles from which they are released in the extracellular space to exert there (signaling) activity. Only recently, another non-classical type of bio-active peptides (NCBAPs) is being discovered. These typically are not secreted but instead appear to be translated from short open reading frames (sORF) and released directly into the cytoplasm. In contrast to CBAPs, they appear to be involved in the regulation of intra-cellular processes such as transcriptional control, calcium handling and DNA repair. However, bio-chemical evidence for the translation of these sORFs remains elusive. Comprehensive analysis of these sORF-encoded polypeptides (SEPs) by peptidomic approach is hampered by a number of methodological and biological challenges: the low molecular mass of SEPs (many are in the range of 4-10 KDa), their low abundance, their transient expression and many complications in data analysis to confidently identify these peptides. In this study, we developed a strategy to address these issues as much as possible. Since translation of these predicted sORFs is still controversial, our data-analysis strategy is aimed not to maximize the number of identifications but rather to exclude as much as possible false positive identifications. Applying this strategy to a mouse brain striatum sample, we identified 981 neuropeptides originated from 50 known (neuro)peptide precursors, demonstrating the sensitivity of the method applied. In addition, five SEPs were identified including NoBody, a SEP that was previously discovered in humans and four novel SEPS from 5’ untranslated transcript regions (UTRs).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Harshavardhan Budamgunta  

LAB HEAD: Geert Baggerman

PROVIDER: PXD008526 | Pride | 2018-05-10

REPOSITORIES: Pride

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Publications

Comprehensive Peptide Analysis of Mouse Brain Striatum Identifies Novel sORF-Encoded Polypeptides.

Budamgunta Harshavardhan H   Olexiouk Volodimir V   Luyten Walter W   Schildermans Karin K   Maes Evelyne E   Boonen Kurt K   Menschaert Gerben G   Baggerman Geert G  

Proteomics 20180501 10


Bio-active peptides are involved in the regulation of most physiological processes in the body. Classical bio-active peptides (CBAPs) are cleaved from a larger precursor protein and stored in secretion vesicles from which they are released in the extracellular space. Recently, another non-classical type of bio-active peptides (NCBAPs) has gained interest. These typically are not secreted but instead appear to be translated from short open reading frames (sORF) and released directly into the cyto  ...[more]

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