
Small humanin-like peptides (SHLPs) are a group of peptides encoded in the
16S ribosomal RNA
16 S ribosomal RNA (or 16 S rRNA) is the RNA component of the 30S subunit of a prokaryotic ribosome ( SSU rRNA). It binds to the Shine-Dalgarno sequence and provides most of the SSU structure.
The genes coding for it are referred to as 16S r ...
region of
mitochondrial
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
genome. Six peptides of this group (SHLP1–6) have been identified so far, each peptide is of 20-38 amino-acid long. They are derived from the mitochondria and act as important
retrograde signaling
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, ins ...
molecules in the cell. Their names were given because the SHLPs share some similar biological effects with the mitochondrial peptide
Humanin
Humanin is a micropeptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry.
In ''in vitro'' and animal models, it appears to have cytoprotective effects. ...
.
Every individual SHLP showed unique expression pattern in mouse tissues. Specifically, SHLP1 was detected in the heart, kidney, and spleen; SHLP2 was detected in the liver, kidney, and muscle; SHLP3 was detected in the brain and spleen; SHLP4 was detected in the liver and prostate; and SHLP6 was detected in the liver and kidney.
Experiments using cultured mammalian cells have shown that SHLPs are bioactive peptides. Incubation of each synthetic SHLP with cells affected cell viability, proliferation and apoptosis differentially, which suggests that every SHLP may play a different role in the biological system.
Discovery
An ''in silico'' search for potential small open-reading-frames (sORFs) within 16S ribosomal RNA-encoding short peptides (20–40 amino acids) was conducted in the
Pinchas Cohen
Pinchas Cohen is the dean of the USC Leonard Davis School of Gerontology, holds the William and Sylvia Kugel Dean's Chair in Gerontology and serves as the executive director of the Ethel Percy Andrus Gerontology Center.
Cohen graduated in 1986 wi ...
lab at University of Southern California. Six sequences encoding 20–38 amino-acid-long peptides were identified, which were named SHLP 1–6. The endogenous SHLPs were detected by
immunoblots and their transcripts were validated by both
qPCR and
northern blot
The northern blot, or RNA blot,Gilbert, S. F. (2000) Developmental Biology, 6th Ed. Sunderland MA, Sinauer Associates. is a technique used in molecular biology research to study gene expression by detection of RNA (or isolated mRNA) in a sample.Ke ...
.
[
]
Structure
All SHLPs, like humanin, are encoded in the mitochondrial 16S RNA gene (MT-RNR2
Mitochondrially encoded 16S RNA (often abbreviated as ''16S'') is the mitochondrial large subunit ribosomal RNA that in humans is encoded by the MT-RNR2 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene ...
). The human[ ] sequences are:[
]
HN MAPRGESCLLLLTSEIDLPVKRRA
S1 MCHWAGGASNTGDARGDVFGKQAG
S2 MGVKFFTLSTREFPSVQRAVPLWTNS
S3 MLGYNFSSFPCGTISIAPGENFYRLYFIWVNGLAKVVW
S4 MLEVMELVNRRGKICRVPETFFNLSL
S5 MYCSEVGFCSEVAPTEIFNAGLWV
S6 MLDQDIPMVQPLLKVRLEND
Note that no formal HUGO gene symbols have been assigned to any of the SHLPs. They are not to be confused with the Shelphs, which are sometimes abbreviated SHLP in their gene symbol.
Functions
Individual SHLPs demonstrated different biological effects. SHLP2 and SHLP3 enhanced cell viability and inhibited apoptosis in both NIT-1 and 22Rv1 cells. SHLP2 and SHLP4 promoted cell proliferation in NIT-1 β-cells. SHLP6 significantly increased apoptosis in both NIT-1 and 22Rv1 cells, having an effect opposite of SHLP2 and SHLP3. Moreover, SHLP2 and SHLP3 also induced oxygen consumption rate (OCR) and increased cellular ATP levels, which indicates that SHLP2 and 3 are mitochondrial modulators.
References
{{CC-notice, cc=by4, url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925829/, author(s)=Laura J. Cobb, Changhan Lee, Jialin Xiao, Kelvin Yen, Richard G. Wong, Hiromi K. Nakamura, Hemal H. Mehta, Qinglei Gao, Carmel Ashur, Derek M. Huffman, Junxiang Wan, Radhika Muzumdar, Nir Barzilai, and Pinchas Cohen2
Metagenomics
HN MAPRGESCLLLLTSEIDLPVKRRA
S1 MCHWAGGASNTGDARGDVFGKOAG
S2 MGVKFFTLSTREFPSVQRAVPLWTNS
S3 MLGYNFSSFPCGTISIAPGENFYRLYFIWVNGLAKVVW
S4 MLEVMELVNRRGKICRVPETFFNLSL
S5 MYCSEVGFCSEVAPTEIFNAGLWV
S6 MLDODIPMVOPLLKVRLEND