TY - JOUR
T1 - Translational control of secretory proteins in health and disease
AU - Karamyshev, Andrey L.
AU - Tikhonova, Elena B.
AU - Karamysheva, Zemfira N.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Secretory proteins are synthesized in a form of precursors with additional sequences at their N-terminal ends called signal peptides. The signal peptides are recognized co-translationally by signal recognition particle (SRP). This interaction leads to targeting to the endoplasmic reticulum (ER) membrane and translocation of the nascent chains into the ER lumen. It was demonstrated recently that in addition to a targeting function, SRP has a novel role in protection of secretory protein mRNAs from degradation. It was also found that the quality of secretory proteins is controlled by the recently discovered Regulation of Aberrant Protein Production (RAPP) pathway. RAPP monitors interactions of polypeptide nascent chains during their synthesis on the ribosomes and specifically degrades their mRNAs if these interactions are abolished due to mutations in the nascent chains or defects in the targeting factor. It was demonstrated that pathological RAPP activation is one of the molecular mechanisms of human diseases associated with defects in the secretory proteins. In this review, we discuss recent progress in understanding of translational control of secretory protein biogenesis on the ribosome and pathological consequences of its dysregulation in human diseases.
AB - Secretory proteins are synthesized in a form of precursors with additional sequences at their N-terminal ends called signal peptides. The signal peptides are recognized co-translationally by signal recognition particle (SRP). This interaction leads to targeting to the endoplasmic reticulum (ER) membrane and translocation of the nascent chains into the ER lumen. It was demonstrated recently that in addition to a targeting function, SRP has a novel role in protection of secretory protein mRNAs from degradation. It was also found that the quality of secretory proteins is controlled by the recently discovered Regulation of Aberrant Protein Production (RAPP) pathway. RAPP monitors interactions of polypeptide nascent chains during their synthesis on the ribosomes and specifically degrades their mRNAs if these interactions are abolished due to mutations in the nascent chains or defects in the targeting factor. It was demonstrated that pathological RAPP activation is one of the molecular mechanisms of human diseases associated with defects in the secretory proteins. In this review, we discuss recent progress in understanding of translational control of secretory protein biogenesis on the ribosome and pathological consequences of its dysregulation in human diseases.
KW - Disease-causing mutations
KW - Human diseases
KW - Protein quality control
KW - Protein synthesis
KW - Protein transport
KW - RNA degradation
KW - Ribosome
KW - Signal recognition particle (SRP)
KW - Signal sequence
KW - Translation regulation
UR - http://www.scopus.com/inward/record.url?scp=85083184017&partnerID=8YFLogxK
U2 - 10.3390/ijms21072538
DO - 10.3390/ijms21072538
M3 - Review article
C2 - 32268488
AN - SCOPUS:85083184017
SN - 1661-6596
VL - 21
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 7
M1 - 2538
ER -