Proteomic Profiling of Unannotated Microproteins in Human Placenta Reveals XRCC6P1 as a Potential Negative Regulator of Translation.
J Proteome Res
; 23(9): 4005-4013, 2024 Sep 06.
Article
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| MEDLINE
| ID: mdl-39171377
ABSTRACT
Ribosome profiling and mass spectrometry have revealed thousands of previously unannotated small and alternative open reading frames (sm/alt-ORFs) that are translated into micro/alt-proteins in mammalian cells. However, their prevalence across human tissues and biological roles remains largely undefined. The placenta is an ideal model for identifying unannotated microproteins and alt-proteins due to its considerable protein diversity that is required to sustain fetal development during pregnancy. Here, we profiled unannotated microproteins and alt-proteins in human placental tissues from preeclampsia patients or healthy individuals by proteomics, identified 52 unannotated microproteins or alt-proteins, and demonstrated that five microproteins can be translated from overexpression constructs in a heterologous cell line, although several are unstable. We further demonstrated that one microprotein, XRCC6P1, associates with translation initiation factor eIF3 and negatively regulates translation when exogenously overexpressed. Thus, we revealed a hidden sm/alt-ORF-encoded proteome in the human placenta, which may advance the mechanism studies for placenta development as well as placental disorders such as preeclampsia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Placenta
/
Preeclampsia
/
Biosíntesis de Proteínas
/
Proteómica
Límite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
J Proteome Res
Asunto de la revista:
BIOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos