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Related Concept Videos

Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
Gene Families01:57

Gene Families

Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...

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Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment
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Published on: September 25, 2017

Evidence for potential functionality of nuclearly-encoded humanin isoforms.

Marek Bodzioch1, Katarzyna Lapicka-Bodzioch, Barbara Zapala

  • 1Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Kopernika 15a, 31-501 Krakow, Poland. mb22@mp.pl

Genomics
|May 30, 2009
PubMed
Summary

Humanin (HN) peptides, derived from mitochondrial genes, show neuroprotective effects. Nuclear gene variants impact HN peptide function and cytoprotection, influencing cell survival pathways.

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An Integrated Approach for Microprotein Identification and Sequence Analysis
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Area of Science:

  • Molecular Biology
  • Neuroscience
  • Genetics

Background:

  • Humanin (HN) is a neuroprotective peptide originating from the mitochondrial MT-RNR2 gene.
  • Emerging evidence suggests nuclear-encoded HN-like peptides exist, potentially regulating cellular functions.
  • Understanding these nuclear variants is crucial for neuroprotection research.

Purpose of the Study:

  • To investigate the existence and characteristics of nuclear-encoded Humanin (HN)-like peptides.
  • To analyze the expression patterns and functional significance of these HN isoforms.
  • To identify key sequence motifs and their roles in HN peptide activity.

Main Methods:

  • Bioinformatic analysis of mitochondrial and nuclear gene sequences.
  • Gene expression profiling in human tissues.
  • Functional assays assessing cytoprotection against apoptosis.
  • Sequence comparison across species to identify conserved motifs.

Main Results:

  • Bioinformatic data suggest 13 MT-RNR2-like nuclear loci encoding 15 distinct HN-like peptides.
  • At least ten nuclear HN genes are expressed in human tissues and respond to staurosporine and beta-carotene.
  • Two consensus motifs (residues 5-11 and 14-19) were identified in nuclear HN isoforms.
  • A variant HN5 peptide with isoleucine at position 13 showed reduced cytoprotection against apoptosis.

Conclusions:

  • The human genome encodes multiple functional Humanin (HN)-like peptides originating from nuclear genes.
  • Specific amino acid residues, such as threonine at position 13, are critical for HN peptide function and receptor binding.
  • Polymorphisms in HN genes can significantly alter cytoprotective efficacy, impacting neurodegenerative disease research.