{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAK16 is an essential gene whose product plays a central role in ribosome biogenesis and cell cycle regulation. In Saccharomyces cerevisiae, Mak16p is a critical component of the pre‐60S ribosomal subunit assembly machinery; it is part of the Nsa1–Rrp1–Rpf1–Mak16 module that stabilizes the solvent side of the maturing 60S particle during early nucleolar assembly (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Disruption of MAK16 function leads to impaired pre–rRNA processing—specifically, a marked reduction in the stability of the 27SB precursor rRNA—and results in decreased levels of free 60S subunits, G1 phase cell cycle arrest, and temperature‐sensitive growth phenotypes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of yeast killer strains, mutations in MAK16 contribute to defective maintenance of M double‐stranded RNA virus–like particles; notably, while suppression by SKI mutations can compensate for many MAK gene defects, the mak16 mutant appears unique in resisting such bypass"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, increased MAK16 transcript levels observed in paf1 mutant backgrounds link its expression to broader transcriptional regulatory networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐established roles in yeast, emerging evidence suggests that MAK16 may have clinical relevance in human disease. Differential expression of MAK16 has been identified among RNA‐binding proteins with prognostic potential in colorectal cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and autoantibodies targeting MAK16 have been incorporated into diagnostic panels for systemic lupus erythematosus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, signals of positive selection at the MAK16 locus have been linked to long‐term adaptation to environmental arsenic exposure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, MAK16 is integral not only to the fundamental process of ribosome assembly and cell cycle progression in yeast but also may serve as a biomarker in human disorders. Its essential function in pre–60S formation—coupled with its impact on rRNA processing, cell growth, and viral RNA maintenance—underscores the multifaceted roles of this gene in both cellular physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lukas Kater, Matthias Thoms, Clara Barrio-Garcia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Visualizing the Assembly Pathway of Nucleolar Pre-60S Ribosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2017.11.039"}], "href": "https://doi.org/10.1016/j.cell.2017.11.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29245012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29245012"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hong Zhang, Yan A Su, Peisheng Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signature patterns revealed by microarray analyses of mice infected with influenza virus A and Streptococcus pneumoniae."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microbes Infect (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.micinf.2006.04.018"}], "href": "https://doi.org/10.1016/j.micinf.2006.04.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16797204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16797204"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "R B Wickner "}, {"type": "b", "children": [{"type": "t", "text": "Host function of MAK16: G1 arrest by a mak16 mutant of Saccharomyces cerevisiae."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (1988)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.85.16.6007"}], "href": "https://doi.org/10.1073/pnas.85.16.6007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "3045810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/3045810"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Y Ohtake, R B Wickner "}, {"type": "b", "children": [{"type": "t", "text": "Yeast virus propagation depends critically on free 60S ribosomal subunit concentration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (1995)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.15.5.2772"}], "href": "https://doi.org/10.1128/MCB.15.5.2772"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7739558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7739558"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "R B Wickner, T J Koh, J C Crowley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation of the MAK16 gene and analysis of an adjacent gene essential for growth at low temperatures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Yeast (1987)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/yea.320030108"}], "href": "https://doi.org/10.1002/yea.320030108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "3332963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/3332963"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "X Shi, A Finkelstein, A J Wolf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paf1p, an RNA polymerase II-associated factor in Saccharomyces cerevisiae, may have both positive and negative roles in transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (1996)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.16.2.669"}], "href": "https://doi.org/10.1128/MCB.16.2.669"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "8552095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/8552095"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xuehui Fan, Lili Liu, Yue Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated analysis of RNA-binding proteins in human colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Surg Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12957-020-01995-5"}], "href": "https://doi.org/10.1186/s12957-020-01995-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32828126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32828126"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hua-Zhi Ling, Shu-Zhen Xu, Rui-Xue Leng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rheumatology (Oxford) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/rheumatology/kez634"}], "href": "https://doi.org/10.1093/rheumatology/kez634"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31899518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31899518"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lucas Vicuña, Mario I Fernandez, Cecilia Vial, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Biol Evol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/gbe/evz172"}], "href": "https://doi.org/10.1093/gbe/evz172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31384924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31384924"}]}]}]}