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RNA (New York, N.Y.) Jan 2019MicroRNAs (miRNAs) are important regulators of gene expression that bind complementary target mRNAs and repress their expression. Precursor miRNA molecules undergo... (Review)
Review
MicroRNAs (miRNAs) are important regulators of gene expression that bind complementary target mRNAs and repress their expression. Precursor miRNA molecules undergo nuclear and cytoplasmic processing events, carried out by the endoribonucleases DROSHA and DICER, respectively, to produce mature miRNAs that are loaded onto the RISC (RNA-induced silencing complex) to exert their biological function. Regulation of mature miRNA levels is critical in development, differentiation, and disease, as demonstrated by multiple levels of control during their biogenesis cascade. Here, we will focus on post-transcriptional mechanisms and will discuss the impact of -acting sequences in precursor miRNAs, as well as -acting factors that bind to these precursors and influence their processing. In particular, we will highlight the role of general RNA-binding proteins (RBPs) as factors that control the processing of specific miRNAs, revealing a complex layer of regulation in miRNA production and function.
Topics: Animals; Cell Nucleus; Cytoplasm; Genetic Variation; Humans; MicroRNAs; RNA Precursors; RNA Processing, Post-Transcriptional; RNA-Binding Proteins; RNA-Induced Silencing Complex; Ribonuclease III
PubMed: 30333195
DOI: 10.1261/rna.068692.118 -
Blood Cancer Journal Jun 2017Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The... (Review)
Review
Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL.
Topics: Female; History, 21st Century; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 28665419
DOI: 10.1038/bcj.2017.53 -
Molecular Cell Mar 2023Biogenesis of mitochondria requires the import of approximately 1,000 different precursor proteins into and across the mitochondrial membranes. Mitochondria exhibit a... (Review)
Review
Biogenesis of mitochondria requires the import of approximately 1,000 different precursor proteins into and across the mitochondrial membranes. Mitochondria exhibit a wide variety of mechanisms and machineries for the translocation and sorting of precursor proteins. Five major import pathways that transport proteins to their functional intramitochondrial destination have been elucidated; these pathways range from the classical amino-terminal presequence-directed pathway to pathways using internal or even carboxy-terminal targeting signals in the precursors. Recent studies have provided important insights into the structural organization of membrane-embedded preprotein translocases of mitochondria. A comparison of the different translocases reveals the existence of at least three fundamentally different mechanisms: two-pore-translocase, β-barrel switching, and transport cavities open to the lipid bilayer. In addition, translocases are physically engaged in dynamic interactions with respiratory chain complexes, metabolite transporters, quality control factors, and machineries controlling membrane morphology. Thus, mitochondrial preprotein translocases are integrated into multi-functional networks of mitochondrial and cellular machineries.
Topics: Mitochondrial Proteins; Mitochondria; Mitochondrial Membranes; Carrier Proteins; Protein Transport; Protein Precursors; Mitochondrial Membrane Transport Proteins
PubMed: 36931257
DOI: 10.1016/j.molcel.2023.02.020 -
Annual Review of Biochemistry Jun 2017Mitochondria are essential organelles with numerous functions in cellular metabolism and homeostasis. Most of the >1,000 different mitochondrial proteins are synthesized... (Review)
Review
Mitochondria are essential organelles with numerous functions in cellular metabolism and homeostasis. Most of the >1,000 different mitochondrial proteins are synthesized as precursors in the cytosol and are imported into mitochondria by five transport pathways. The protein import machineries of the mitochondrial membranes and aqueous compartments reveal a remarkable variability of mechanisms for protein recognition, translocation, and sorting. The protein translocases do not operate as separate entities but are connected to each other and to machineries with functions in energetics, membrane organization, and quality control. Here, we discuss the versatility and dynamic organization of the mitochondrial protein import machineries. Elucidating the molecular mechanisms of mitochondrial protein translocation is crucial for understanding the integration of protein translocases into a large network that controls organelle biogenesis, function, and dynamics.
Topics: Carrier Proteins; Eukaryotic Cells; Gene Expression; Humans; Isoenzymes; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Membranes; Mitochondrial Precursor Protein Import Complex Proteins; Mitochondrial Proteins; Organelle Biogenesis; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Precursors; Protein Transport
PubMed: 28301740
DOI: 10.1146/annurev-biochem-060815-014352 -
International Journal of Molecular... Dec 2022Amyloidoses are a group of diseases associated with deposits of amyloid fibrils in different tissues. So far, 36 different types of amyloidosis are known, each due to... (Review)
Review
Amyloidoses are a group of diseases associated with deposits of amyloid fibrils in different tissues. So far, 36 different types of amyloidosis are known, each due to the misfolding and accumulation of a specific protein. Amyloid deposits can be found in several organs, including the heart, brain, kidneys, and spleen, and can affect single or multiple organs. Generally, amyloid-forming proteins become prone to aggregate due to genetic mutations, acquired environmental factors, excessive concentration, or post-translational modifications. Interestingly, amyloid aggregates are often composed of proteolytic fragments, derived from the degradation of precursor proteins by yet unidentified proteases, which display higher amyloidogenic tendency compared to precursor proteins, thus representing an important mechanism in the onset of amyloid-based diseases. In the present review, we summarize the current knowledge on the proteolytic susceptibility of three of the main human amyloidogenic proteins, i.e., transthyretin, β-amyloid precursor protein, and α-synuclein, in the onset of amyloidosis. We also highlight the role that proteolytic enzymes can play in the crosstalk between intestinal inflammation and amyloid-based diseases.
Topics: Humans; Proteolysis; Amyloidosis; Amyloid; Amyloid beta-Protein Precursor; Protein Precursors; Prealbumin; Peptide Hydrolases
PubMed: 36614141
DOI: 10.3390/ijms24010699 -
The FEBS Journal Jul 2022Coordination of transcription and processing of RNA is a basic principle in regulation of gene expression in eukaryotes. In the case of mRNA, coordination is primarily... (Review)
Review
Coordination of transcription and processing of RNA is a basic principle in regulation of gene expression in eukaryotes. In the case of mRNA, coordination is primarily founded on a co-transcriptional processing mechanism by which a nascent precursor mRNA undergoes maturation via cleavage and modification by the transcription machinery. A similar mechanism controls the biosynthesis of rRNA. However, the coordination of transcription and processing of tRNA, a rather short transcript, remains unknown. Here, we present a model for high molecular weight initiation complexes of human RNA polymerase III that assemble on tRNA genes and process precursor transcripts to mature forms. These multifunctional initiation complexes may support co-transcriptional processing, such as the removal of the 5' leader of precursor tRNA by RNase P. Based on this model, maturation of tRNA is predetermined prior to transcription initiation.
Topics: Humans; RNA Polymerase III; RNA Precursors; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Transfer; Ribonuclease P; Transcription, Genetic
PubMed: 33929081
DOI: 10.1111/febs.15904 -
The Journal of Investigative Dermatology Jan 2023Deciphering the pathways that regulate human epidermal precursor cell fate is necessary for future developments in skin repair and graft bioengineering. Among them,...
Deciphering the pathways that regulate human epidermal precursor cell fate is necessary for future developments in skin repair and graft bioengineering. Among them, characterization of pathways regulating the keratinocyte (KC) precursor immaturity versus differentiation balance is required for improving the efficiency of KC precursor ex vivo expansion. In this study, we show that the transcription factor MXD4/MAD4 is expressed at a higher level in quiescent KC stem/progenitor cells located in the basal layer of human epidermis than in cycling progenitors. In holoclone KCs, stable short hairpin-RNA‒mediated decreased expression of MXD4/MAD4 increases MYC expression, whose modulation increases the proliferation of KC precursors and maintenance of their clonogenic potential and preserves the functionality of these precursors in three-dimensional epidermis organoid generation. Altogether, these results characterize MXD4/MAD4 as a major piece of the stemness puzzle in the human epidermis KC lineage and pinpoint an original avenue for ex vivo expansion of human KC precursors.
Topics: Humans; Cell Differentiation; Epidermal Cells; Epidermis; Keratinocytes; Basic Helix-Loop-Helix Transcription Factors
PubMed: 36007550
DOI: 10.1016/j.jid.2022.07.020 -
The FEBS Journal Nov 2022Most chloroplast proteins are nucleus-encoded, translated on cytoplasmic ribosomes as precursor proteins, and imported into chloroplasts through TOC and TIC, the... (Review)
Review
Most chloroplast proteins are nucleus-encoded, translated on cytoplasmic ribosomes as precursor proteins, and imported into chloroplasts through TOC and TIC, the translocons of the outer and inner chloroplast envelope membranes. While the composition of the TOC complex is well established, there is still some controversy about the importance of a recently identified TIC complex consisting of Tic20, Tic214, Tic100, and Tic56. TOC and TIC form a supercomplex with a protein channel at the junction of the outer and inner envelope membranes through which preproteins are pulled into the stroma by the ATP-powered Ycf2 complex consisting of several FtsH-like ATPases and/or by chloroplast Hsp proteins. Several components of the TOC/TIC system are moonlighting proteins with additional roles in chloroplast gene expression and metabolism. Chaperones and co-chaperones, associated with TOC and TIC on the cytoplasmic and stromal side of the chloroplast envelope, participate in the unfolding and folding of the precursor proteins and act together with the ubiquitin-proteasome system in protein quality control. Chloroplast protein import is also intimately linked with retrograde signaling, revealing altogether an unsuspected complexity in the regulation of this process.
Topics: Plant Proteins; Chloroplasts; Chloroplast Proteins; Protein Transport; Molecular Chaperones; Protein Precursors
PubMed: 35472255
DOI: 10.1111/febs.16464 -
ACS Applied Materials & Interfaces Aug 2023The maskless and chemical-free conversion and patterning of synthetic polymer precursors into laser-induced graphene (LIG) via laser-induced pyrolysis is a relatively... (Review)
Review
The maskless and chemical-free conversion and patterning of synthetic polymer precursors into laser-induced graphene (LIG) via laser-induced pyrolysis is a relatively new but growing field. Bioderived precursors from lignocellulosic materials can also be converted to LIG, opening a path to sustainable and environmentally friendly applications. This review is designed as a starting point for researchers who are not familiar with LIG and/or who wish to switch to sustainable bioderived precursors for their applications. Bioderived precursors are described, and their performances (mainly crystallinity and sheet resistance of the obtained LIG) are compared. The three main fields of application are reviewed: supercapacitors and electrochemical and physical sensors. The key advantages and disadvantages of each precursor for each application are discussed and compared to those of a benchmark of polymer-derived LIG. LIG from bioderived precursors can match, or even outperform, its synthetic analogue and represents a viable and sometimes better alternative, also considering its low cost and biodegradability.
PubMed: 37471123
DOI: 10.1021/acsami.3c07687 -
Clinical Pathology (Thousand Oaks,... 2020Cholangiocarcinoma (CCA) develops through multistep carcinogenesis. During the past decades, 2 precursors have been proved to evolve to CCA. The 2 main precursor lesions... (Review)
Review
Cholangiocarcinoma (CCA) develops through multistep carcinogenesis. During the past decades, 2 precursors have been proved to evolve to CCA. The 2 main precursor lesions of CCA are biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. It is an interesting and relatively novel entity for the hepatobiliary surgeons, radiologists, oncologists, and pathologists. It worth being familiar with these 2 entities for better communication between pathologists, oncologists, and surgeons to improve the treatment and follow-up of these lesions, which can definitely decrease their evolvement to CCA as an aggressive, poor prognostic, and life-threatening cancer. In this narrative review, I collected and discussed all published studies about these 2 precursor lesions of CCA including radiologic, clinical, and pathological manifestation.
PubMed: 32596664
DOI: 10.1177/2632010X20925045