High-fidelity protein localization is essential to define the identities and functions of different organelles and to maintain cellular homeostasis. Accurate localization of nascent proteins requires specific protein targeting pathways as well as quality control (QC) mechanisms to remove mislocalized proteins. The endoplasmic reticulum (ER) is the first destination for approximately one-third of the eukaryotic proteome and a major site of protein biosynthesis and QC. In mammalian cells, trafficking from the ER provides nascent proteins access to the extracellular space and essentially every cellular membrane and organelle except for mitochondria and possibly peroxisomes. Here, we discuss the biosynthetic mechanisms that deliver nascent proteins to the ER and the QC mechanisms that interface with the ER to correct or degrade mislocalized proteins.
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http://dx.doi.org/10.1101/cshperspect.a041249 | DOI Listing |
Genes Dev
January 2025
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095, USA;
The Rbfox proteins regulate alternative pre-mRNA splicing by binding to the RNA element GCAUG. In the nucleus, most of Rbfox is bound to the large assembly of splicing regulators (LASR), a complex of RNA-binding proteins that recognize additional RNA motifs. However, it remains unclear how the different subunits of the Rbfox/LASR complex act together to bind RNA and regulate splicing.
View Article and Find Full Text PDFMol Biol Cell
January 2025
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nearly all mitochondrial proteins are imported into mitochondria from the cytosol. How nascent mitochondrial precursors acquire and sustain import-competence in the cytosol under normal and stress conditions is incompletely understood. Here, we show that under normal conditions, the Hsc70 and Hsp90 systems interact with and redundantly minimize precursor degradation.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 573 Xujiahui Road, Huangpu District, Shanghai 200025, China.
Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/-mice and cells, both of which exhibited dramatic mitochondrial changes.
View Article and Find Full Text PDFProtein synthesis is by far the most energetically costly cellular process in rapidly dividing cells. Quantifying translating ribosomes in individual cells and their average mRNA transit rate is arduous. Quantitating assembled ribosomes in individual cells requires electron microscopy and does not indicate ribosome translation status.
View Article and Find Full Text PDFCurr Protein Pept Sci
January 2025
Department of Pharmacy, Panipat Institute of Engineering and Technology, India.
The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders.
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