bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2025–02–16
two papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Rapid quantification of intracellular calcium stores reveals effects of membrane micropeptides on SERCA function.
  2. AUGcontext DB: a comprehensive catalog of the mRNA AUG initiator codon context across eukaryotes.
  1. Cell Calcium. 2025 Feb 07. pii: S0143-4160(25)00009-0. [Epub ahead of print]126 103000
    Rapid quantification of intracellular calcium stores reveals effects of membrane micropeptides on SERCA function.
    Jacob D Cunningham, Taylor A Phillips, Jaroslava Seflova, Ellen E Cho, Seth L Robia.
      To determine how regulation of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) affects the Ca2+ content of the endoplasmic reticulum (ER), we developed a ratiometric ER-localized Ca2+ indicator to rapidly quantify Ca2+ stores and assess SERCA function in live cells. This assay enables screening of membrane micropeptides and small molecules that modulate SERCA and Na+/K+-ATPase activity and may facilitate development of therapies that target cellular Ca2+ handling. Of the micropeptides tested, phospholamban (PLB) had the greatest degree of inhibition of SERCA, as measured by a decrease in ER Ca2+ content compared to control. Sarcolipin (SLN), endoregulin (ELN), and another-regulin (ALN) also decreased ER Ca2+ content, though less potently than PLB. We also investigated micropeptides that have been shown to have a positive effect on ER Ca2+ uptake. Dwarf open reading frame (DWORF), a positive modulator of SERCA activity, and phospholemman (PLM), an inhibitor of the Na+/K+-ATPase, both increased ER Ca2+ content compared to control. A superinhibitory variant of PLM, R70C, further increased ER Ca2+ load compared to wild type PLM. Overall, our findings indicate that the inhibitory potency of micropeptides is governed by their relative binding affinities to SERCA. This allows for finely tuned modulation of Ca2+ handling in different tissues based on differential expressions of micropeptide species. Understanding the contribution of each micropeptide to SERCA regulation may reveal novel strategies for therapeutic intervention in conditions where calcium dysregulation plays a role, such as heart disease, vascular disease, or neurodegenerative disorders.
    Keywords:  Calcium signaling; Calcium transporter; Genetically-encoded calcium indicators; Micropeptides; SERCA
    DOI:  https://doi.org/10.1016/j.ceca.2025.103000
  2. RNA Biol. 2025 Dec;22(1): 1-5
    AUGcontext DB: a comprehensive catalog of the mRNA AUG initiator codon context across eukaryotes.
    Vincent G Osnaya, Laura Gómez-Romero, Gabriel Moreno-Hagelsieb, Greco Hernández.
      The mRNA translation defines the composition of the cell proteome in all forms of life and diseases. In this process, precise selection of the mRNA translation initiation site (TIS) is crucial, as it establishes the correct open reading frame for triplet decoding. We have gathered and curated all published TIS consensus context sequences. We also included the TIS consensus context from novel 538 fungal genomes available from NCBI's RefSeq database. To do so, we wrote ad hoc programs in PERL to find and extract the TIS for each annotated gene, plus ten bases upstream and three downstream. For each genome, the sequences around the TIS of each gene were obtained, and the consensus was further calculated according to the Cavener rules and by the LOGOS algorithm. We created AUGcontext DB, a portal with a comprehensive collection of TIS context sequences across eukaryotes in a range from -10 to + 6. The compilation covers species of 30 vertebrates, 17 invertebrates, 25 plants, 14 fungi, and 11 protists studied in silico; 23 experimental studies; data on biotechnology; and the discovery of 8 diseases associated with specific mutations. Additionally, TIS context sequences of cellular IRESs were included. AUGcontext DB belongs to the National Institute of Cancer (Instituto Nacional de Cancerología, INCan), Mexico, and is freely available at http://108.161.138.77:8096/. Our catalogue allows us to do comparative studies between species, may help improve the diagnosis of certain diseases, and will be key to maximize the production of recombinant proteins.
    Keywords:  AUG codon; Kozak motif; Translation initiation site; fungal translation; translational control
    DOI:  https://doi.org/10.1080/15476286.2025.2465196
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