Micropeptide
Micropeptides (also referred to as microproteins) are polypeptides with a length of less than 100-150 amino acids that are encoded by short open reading frames (sORFs).
[1][4] In terms of size, micropeptides are considerably shorter than "canonical" proteins, which have an average length of 330 and 449 amino acids in prokaryotes and eukaryotes, respectively.
For example, the translated product of an upstream open reading frame (uORF) might be called a uORF-encoded peptide (uPEP).
One regulatory function is that of peptoswitches, which inhibit expression of downstream coding sequences by stalling ribosomes, through their direct or indirect activation by small molecules.
RNA-Seq uses next-generation sequencing (NGS) to determine which RNAs are expressed in a given cell, tissue, or organism at a specific point in time.
[1] Because of the strong likelihood of sORFs less than 100 aa occurring by chance, further study is necessary to determine the validity of data obtained using this method.
[11] Ribosome profiling has been used to identify potential micropeptides in a growing number of organisms, including fruit flies, zebrafish, mice and humans.
Custom antibodies targeted to the micropeptide of interest can be useful for quantifying expression or determining intracellular localization.
[2] Genome editing can be used to add FLAG/MYC or other small peptide tags to an endogenous sORF, thus creating fusion proteins.
[9] The 46 aa Sda micropeptide, expressed by B. subtilis, represses sporulation when replication initiation is impaired.
By inhibiting the histidine Kinase KinA, Sda prevents the activation of the transcription factor Spo0A, which is required for sporulation.
[10] In S. aureus, there are a group of micropeptides, 20-22 aa, that are excreted during host infection to disrupt neutrophil membranes, causing cell lysis.
This micropeptide interacts with developmental PIN proteins to form a critical network for hormonal crosstalk between auxin, ethylene, and cytokinin.
The mechanism of ROT4 function is not well understood, but mutants have short rounded leaves, indicating that this peptide may be important in leaf morphogenesis.
[30] The evolutionarily conserved polished rice (pri) gene, known as tarsal-less (tal) in D. melanogaster, is involved in epidermal differentiation.
This converts Svb into an activator that directly regulates the expression of target effectors, including miniature (m) and shavenoid (sha), which are together responsible for trichome formation.
Although it was annotated as a lncRNA in zebrafish, mouse, and human, the 58-aa ORF was found to be highly conserved among vertebrate species.
Similarly, the endoregulin (ELN) and another-regulin (ALN) genes code for transmembrane micropeptides that contain the SERCA binding motif, and are conserved in mammals.
[7] Myomixer (Mymx) is encoded by the gene Gm7325, a muscle-specific peptide, 84 aa in length, which plays a role during embryogenesis in fusion and skeletal muscle formation.
[8] In humans, NoBody (non-annotated P-body dissociating polypeptide), a 68 aa micropeptide, was discovered in the long intervening noncoding RNA (lincRNA) LINC01420.
APELA) is an endogenous hormone that is secreted as a 32 amino acid micropeptide by human embryonic stem cells.
[37] In differentiating mesoendermal cells ELA binds to, and signals via, APLNR, a GPCR which can also respond to the hormonal peptide APLN.
The second predicted micropeptide, MRI-2, may be important in non-homologous end joining (NHEJ) of DNA double strand breaks.
[39] A micropeptide of 90aa, ‘Small Regulatory Polypeptide of Amino Acid Response’ or SPAAR, was found to be encoded in the lncRNA LINC00961.
Down-regulation of this micropeptide enables mTORC1 activation by amino acid stimulation, promoting muscle regeneration.
[40] This article was adapted from the following source under a CC BY 4.0 license (2018) (reviewer reports): Maria E. Sousa; Michael H. Farkas (13 December 2018).
