The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth

Bai, Dongmei; Zhang, Jinfang; Li, Tingting; Hang, Runlai; Liu, Yong; Tian, Yonglu; Huang, Dadu; Cao, Xiaofeng; Ji, Jiafu; Zheng, Xiaofeng

doi:10.1038/ncomms12310

Cited by 36 publications

(52 citation statements)

References 43 publications

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“…Interestingly, the molecular mechanism proposed here ( Figure 8) shows striking parallels to the late stages of the cytosolic/archeal SSU biogenesis catalysed by the adenylate kinase Fap7/hCINAP (92).…”

Section: Discussionmentioning

confidence: 54%

YBEY is an essential biogenesis factor for mitochondrial ribosomes

Summer

Smirnova

Gabriele

et al. 2019

Preprint

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Ribosome biogenesis requires numerous trans-acting factors, some of which are deeply conserved. In Bacteria, the endoribonuclease YbeY is believed to be involved in 16S rRNA 3'-end processing and its loss was associated with ribosomal abnormalities. In Eukarya, YBEY appears to generally localize to mitochondria (or chloroplasts). Here we show that the deletion of human YBEY results in a severe respiratory deficiency and morphologically abnormal mitochondria as an apparent consequence of impaired mitochondrial translation. Reduced stability of 12S rRNA and the deficiency of several proteins of the small ribosomal subunit in YBEY knockout cells pointed towards a defect in mitochondrial ribosome biogenesis. The specific interaction of mitoribosomal protein uS11m with YBEY suggests that the latter recruits uS11m to the nascent small subunit in its late assembly stage. This scenario shows similarities with final stages of cytosolic ribosome biogenesis, and may represent a late checkpoint before the mitoribosome engages in translation. INTRODUCTIONRibosome biogenesis is a highly complex process that starts co-transcriptionally and includes ribosomal RNA processing, modification, and binding of ribosomal proteins (1). Each of these steps relies on specific factors, some of which are remarkably conserved. One such factor is the UPF0054 family protein YbeY found in all classified bacteria (2). Based on studies in various bacteria, YbeY has been implicated in ribosome maturation and quality control, with a particularly important role in small subunit (SSU) biogenesis (3-8), and post-transcriptional gene expression regulation (9-14). The deletion of ybeY is often lethal or associated with severe alterations of cellular metabolism and growth, indicating its indispensability for a wide variety of bacterial-type ribosomes (4,6,7,(13)(14)(15)(16)(17).Mechanistically, YbeY has been described as a metal-dependent endoribonuclease (5,12), and in some bacteria, ybeY mutants accumulate 16S rRNA with an unprocessed 3' end (3,5,7,8). Therefore, YbeY was proposed to be the "missing" 3' endoribonuclease required for 16S rRNA maturation to obtain the correct anti-Shine-Dalgarno sequence, which is needed for translation initiation on most bacterial mRNAs. However, this 16S rRNA 3'-misprocessing phenotype could equally be caused by the loss of a ribosome biogenesis factor that is not per se involved in rRNA cleavage (18), and so the precise role of YbeY in ribosome biogenesis remains unclear.By carrying out an in-depth phylogenetic analysis, we found that YBEY is also conserved in many eukaryal lineages, including animals, plants, most stramenopiles and alveolates (Supplementary Figure 1). Indeed, YbeY of Arabidopsis thaliana was reported to be an essential ribosome biogenesis factor in chloroplasts, and its absence was associated with severe misprocessing of nearly all chloroplast rRNAs, resulting in deficiency of organellar translation, and hence, the absence of photosynthesis (16). Human YBEY, which shares 27% of identity with YbeY of...

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Section: Discussionmentioning

confidence: 54%

YBEY is an essential biogenesis factor for mitochondrial ribosomes

Summer

Smirnova

Gabriele

et al. 2019

Preprint

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“…Matched pairs of primary tumors and liver metastases are 18. IHC analysis was performed by Outdo Biotech (Shanghai, China) using standard techniques as described 29 . Briefly, all specimens on the tissue microarray were evaluated by H&E (hematoxylin-eosin) staining to ensure the pathological types before IHC staining.…”

Section: Methodsmentioning

confidence: 99%

“…The degree of immunostaining was scored by two independent investigators without prior knowledge of the clinical data. The IHC scores were calculated as previously described 29 . In brief, more than 1,000 tumor cells for each sample were analyzed under microscope.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Reprogramming of Tissue-Specific Transcription Promotes Metastasis

Teng

Yang

et al. 2017

Preprint

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13Tumor metastasis is the cause of death for 90% of cancer patients, and no 14 currently-available therapies target this multi-step process in which cancer cells 15 spread from the local tissue of a primary tumor to distant organs where they 16 establish secondary tumors 1 . Although epithelial-to-mesenchymal transition 2 , 17 tumor-secreted exosomes 3 , epigenetic regulators as well as other genes 4-8 have 18 been implicated in metastasis, little is known about how cells adapt to and 19 colonize new tissue environments. Here, we show that the epigenetics-mediated 20reprogramming of tissue-specific gene transcription in cancer cells promotes 21 metastasis. Using colorectal cancer (CRC) as a model, we found in both clinical 22 3 reprogramming in several cohorts of clinical CRC tumor samples and in multiple 33 other forms of metastatic cancers, indicate that this reprogramming may be a 34 common feature of metastasis in multiple cancers and suggest the targeted 35 disruption of this epigenetic reprogramming as a strategy for the development of 36 therapies to treat metastasis, the leading cause of cancer-related mortality. 37 MAIN 39Tumor metastasis refers to the movement of tumor cells from a primary site 40to distant organs that they progressively colonize 9 . More than 100 years ago, 41Paget suggested the idea of metastasis as the interaction of "seeds" and "soil" 10 , 42 but subsequent research has yielded only a limited understanding of the 43 mechanism(s) through which metastatic cancer cells ("seeds") adapt to and 44 colonize a new tissue environment ("soil"), the crucial steps of the metastasis 45 process 11 . 46It has been reported that the expression of tissue-specific or cell-lineage 47 7 the genome regions around loci encoding up-regulated liver-specific genes had 113 enriched H3K27ac (P value = 2.2e-16, by t-test) and H3K4me2 (P value = 2.2e-16, 114 by t-test) deposition (Fig. 2c). 115So-called super-enhancers are a small fraction of total enhancers and 116 encompass broad chromatin domains with H3K27ac deposition near genes 117 essential for defining cell identity 20,21 . By identifying super-enhancers in SW480 118 and SW620 cells based on our H3K27ac ChIP-seq datasets, we found that in 119 addition to the 264 super-enhancers common to both cell lines, there are 280 and 120 215 unique super-enhancers in SW620 and SW480 cells, respectively (Extended 121 Data Fig. 4d). Comparison between our ChIP-seq and RNA-seq data revealed a 122 high Pearson correlation coefficient (R = 0.807, P value < 2.2e-16) between the 123 genome-wide distribution of super-enhancers and the expression levels of the 124 nearest genes in these two cell lines ( Fig. 2d and Extended Data Fig. 4e). Notably, 125 many of the liver-specific genes in SW620 cells were found near SW620-unique 126 super-enhancers; while the colon-specific genes in SW480 cells were found close 127 to SW480-unique super-enhancers ( Fig. 2e and Extended Data Fig. 4f, g). Our 128 epigenetic and transcriptomics experiments demonstrate that reshaped enhancer 129 ...

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“…While no interaction was observed between Nob1 and Fap7 in yeast , Fap7 homologue – hCINAP – interacts with NOB1 in human cells. Intriguingly, in contrast to the archaeal counterpart, hCINAP ATPase activity is required for stimulation of intrinsically weak NOB1 endoribonuclease properties . The reason for such divergence in the Fap7/hCINAP roles between organisms deserves deeper exploration in the future.…”

Section: Enzymes Involved In Pre‐rrna Processing In Various Eukaryotesmentioning

confidence: 99%

“…1; Table S1). The endoribonucleolytic activity has been demonstrated for S. cerevisiae and A. thaliana Nob1, and very recently also for the human protein, however, in the latter case it was detectable in vitro only in the presence of an active ATPase cofactor, hCINAP [17,18,28,29,167,171,172].…”

Section: Nob1mentioning

confidence: 99%

Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo‐ and exoribonucleases

2017

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Edited by Michael IbbaProper regulation of ribosome biosynthesis is mandatory for cellular adaptation, growth and proliferation. Ribosome biogenesis is the most energetically demanding cellular process, which requires tight control. Abnormalities in ribosome production have severe consequences, including developmental defects in plants and genetic diseases (ribosomopathies) in humans. One of the processes occurring during eukaryotic ribosome biogenesis is processing of the ribosomal RNA precursor molecule (pre-rRNA), synthesized by RNA polymerase I, into mature rRNAs. It must not only be accurate but must also be precisely coordinated with other phenomena leading to the synthesis of functional ribosomes: RNA modification, RNA folding, assembly with ribosomal proteins and nucleocytoplasmic RNP export. A multitude of ribosome biogenesis factors ensure that these events take place in a correct temporal order. Among them are endo-and exoribonucleases involved in pre-rRNA processing. Here, we thoroughly present a wide spectrum of ribonucleases participating in rRNA maturation, focusing on their biochemical properties, regulatory mechanisms and substrate specificity. We also discuss cooperation between various ribonucleolytic activities in particular stages of pre-rRNA processing, delineating major similarities and differences between three representative groups of eukaryotes: yeast, plants and humans.Keywords: endoribonuclease; exoribonuclease; pre-rRNA processing; ribosome biogenesis; RNA quality control; RNA trimming Ribosome biosynthesis is a multistep process that includes several tightly controlled events -ribosomal DNA (rDNA) transcription, processing of rRNA precursors into mature molecules, accompanied by binding of ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs), and the final assembly of all Abbreviations CD, catalytic domain; dsRBD, double-stranded RNA-binding domain; ETS, external transcribed spacer; ITS, internal transcribed spacer; LSU, large ribosome subunit (60S); miRNA, microRNA; mRNA, messenger RNA; MRP RNA, noncoding RNA component of the RNase MRP; mTOR, mammalian target of rapamycin; nt(s), nucleotide(s); PIN domain, PilT N-terminal domain; Pol I/II/III, RNA polymerase I/II/III; prerRNA, ribosomal RNA precursor; RBF, ribosome biogenesis factor; RMRP, RNase MRP (mitochondrial RNA processing ribonuclease); RNase, ribonuclease; RNB domain, RNase II domain; RNP, ribonucleoprotein; RP, ribosomal protein; rRNA, ribosomal RNA; siRNA, short interfering RNA; snoRNA, small nucleolar RNA; snoRNP, small nucleolar ribonucleoprotein; snRNA, small nuclear RNA; SSU, small ribosome subunit (40S); TRAMP4 or TRAMP5, Trf4/Air/Mtr4 or Trf5/Air/Mtr4 polyadenylation complex; tRNA, transfer RNA.

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The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth

Cited by 36 publications

References 43 publications

YBEY is an essential biogenesis factor for mitochondrial ribosomes

YBEY is an essential biogenesis factor for mitochondrial ribosomes

Epigenetic Reprogramming of Tissue-Specific Transcription Promotes Metastasis

Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo‐ and exoribonucleases

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