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Review
. 2023 Jun 22:11:1186638.
doi: 10.3389/fcell.2023.1186638. eCollection 2023.

The coordinated management of ribosome and translation during injury and regeneration

Thanh Nguyen  1 , Jason C Mills  1   2   3 , Charles J Cho  1
Affiliations
Review

The coordinated management of ribosome and translation during injury and regeneration

Thanh Nguyen et al. Front Cell Dev Biol. .

Abstract

Diverse acute and chronic injuries induce damage responses in the gastrointestinal (GI) system, and numerous cell types in the gastrointestinal tract demonstrate remarkable resilience, adaptability, and regenerative capacity in response to stress. Metaplasias, such as columnar and secretory cell metaplasia, are well-known adaptations that these cells make, the majority of which are epidemiologically associated with an elevated cancer risk. On a number of fronts, it is now being investigated how cells respond to injury at the tissue level, where diverse cell types that differ in proliferation capacity and differentiation state cooperate and compete with one another to participate in regeneration. In addition, the cascades or series of molecular responses that cells show are just beginning to be understood. Notably, the ribosome, a ribonucleoprotein complex that is essential for translation on the endoplasmic reticulum (ER) and in the cytoplasm, is recognized as the central organelle during this process. The highly regulated management of ribosomes as key translational machinery, and their platform, rough endoplasmic reticulum, are not only essential for maintaining differentiated cell identity, but also for achieving successful cell regeneration after injury. This review will cover in depth how ribosomes, the endoplasmic reticulum, and translation are regulated and managed in response to injury (e.g., paligenosis), as well as why this is essential for the proper adaptation of a cell to stress. For this, we will first discuss how multiple gastrointestinal organs respond to stress through metaplasia. Next, we will cover how ribosomes are generated, maintained, and degraded, in addition to the factors that govern translation. Finally, we will investigate how ribosomes and translation machinery are dynamically regulated in response to injury. Our increased understanding of this overlooked cell fate decision mechanism will facilitate the discovery of novel therapeutic targets for gastrointestinal tract tumors, focusing on ribosomes and translation machinery.

Keywords: injury; paligenosis; regeneration; ribosome; translation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Overview of the biogenesis and translation of ribosomes during homeostasis. Ribosomal DNA (rDNA) transcription occurs in the nucleolus by RNA polymerase I. 18S rRNA is a component of the 40S small subunit (SSU), while 5.8S and 28S rRNA generates the 60S large subunit (LSU), along with 5S rRNA transcribed in the nucleoplasm. mRNAs and ribosomal proteins are transcribed by RNA polymerase II together with initiation factors and template mRNAs. In addition, RNA polymerase III generates tRNAs and 7SL-RNA in the nucleoplasm. SSUs undergo substantial modifications en route to the cytoplasm, where they encounter mRNA, initiation factors, and initiator methionine tRNA to form a preinitiation complex, followed by addition of 60S LSU to form 80S ribosome, also known as the monosome. The monosome can be translated in the cytoplasm as is or can form a polysome to generate nascent peptides more efficiently (cytosolic translation). On the other hand, mRNAs containing a signal sequence can translocate to the endoplasmic reticulum with the guidance of the signal recognition particle (SRP) complex as a monosome to produce secretory or membrane-bound peptides requiring extensive post-translational modification. Also, de novo translation initiation can occur on ER.
FIGURE 2
FIGURE 2
Pathways of ribosome regulation during injury (1) During stress, multiple kinases phosphorylate the Serine 51 residue of eIF2 alpha, reducing translation efficiency. The stalled preinitiation complex can be localized to membraneless granules, such as stress granules. (2) Ribosome degradation can be prevented by ribosome-plugging proteins (green circles), the majority of which are evolutionarily conserved. (3) Ribosomes in the cytosol and those attached to the rough ER are susceptible to autophagic destruction through ribophagy and reticulophagy. (4) Ribosomal proteins (such as RPL5 and 11) and 5S ribosomal RNA complex (5S RNP) from degraded ribosomes or other errors in ribosome biogenesis stabilize p53 by sequestering and inhibiting MDM2, ultimately blocking cell cycle progression.
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