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Keywords {🔍}

zfas, expression, cells, cell, cancer, breast, figure, ribosome, additional, file, fig, authors, rna, ribosomal, ribosomes, shrna, pubmed, data, article, protein, normal, genes, lines, fractions, rps, isoforms, google, scholar, lncrnas, znfx, samples, mdamb, shown, analysis, subunit, knockdown, biogenesis, comments, function, noncoding, abundance, response, rrna, found, cas, reviewer, long, lncrna, mammary, synthesis,

Topics {✒️}

ice-cold phosphate-buffered saline kaplan-meier plot generated article download pdf ribo-seq genome browser m-mlv reverse transcriptase lacking protein-coding potential diamond-blackfan anemia results multi-small-nucleolar-rna bba-mol cell res annotated protein-coding genes 50 mm tris–hcl ph 7 20 mm tris–hcl ph 7 5 mm tris–hcl ph 7 primer set e1f1-e2r2 primer set e1f3-e5r1 mda-mb-468 cell lysates forming polypeptide-puromycin derivatives mda-mb-468 cell line zinc finger nfx-1-type open reading frame transfected mda-mb-468 cells her2-positive breast cancer necessarily matched-normal samples developmental protein-coding genes mda-mb-468 cell extracts treated mda-mb-468 cells results protein-coding potential david cameron-smith mda-mb-468 cellular fractions ribosomal rna-protein complexes ribosome-interacting mechanism pertaining phospho-s6 ribosomal protein mann whitney test mda-mb-468 polysome gradients full size image privacy choices/manage cookies triana-alonso fj cis-acting noncoding rnas snord-host rna zfas1 mouse mammary gland nat rev cancer creative commons license nonsense-mediated decay full access ribosome search search mammary gland ducts mol cell biol 60 mm tris–hcl nat chem biol uncut immunoblot image

Questions {❓}

• (2) Figure 1b: can the authors exclude (experimentally) that the difference in expression of ZFAS1 and ZNFX1 is due to different primer efficiency?
• (7) Given that BC2 sequence enables a 50% knockdown of ZFAS1, wouldn’t the authors expect only a partial blockage of 45S rRNA synthesis in their cells upon expression of BC2?
• , RNA, 2011)?
• Also why is it important to determine the relative expression difference between ZFAS1 and ZNFX1?
• Are snoRNAs and snoRNA host genes new players in cancer?
• Does the ribosome translate cancer?
• How would they interpret these results?
• Ribosome biogenesis: achilles heel of cancer?
• This view is a bit simplistic and not very convincing at this stage, can the authors explain better and provide a stronger rationale that will help the reader understand the main reasons for investigating this gene?
• What do the authors conclude, other that ZFAS1 and ZNFX1 are expressed in both normal and cancer?
• Which primer pair was used in these figures?

Schema {🗺️}

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         headline:ZFAS1: a long noncoding RNA associated with ribosomes in breast cancer cells
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      headline:ZFAS1: a long noncoding RNA associated with ribosomes in breast cancer cells
      description:Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts including thousands of lncRNAs that generally lack protein coding potential. However, only a small percentage of these molecules has been functionally characterised, and discoveries of specific functions demonstrate layers of complexity. A large percentage of lncRNAs is located in the cytoplasm, associated with ribosomes but the function of the majority of these transcripts is unclear. The current study analyses putative mechanisms of action of the lncRNA species member ZFAS1 that was initially discovered by microarray analysis of murine tissues undergoing mammary gland development. As developmental genes are often deregulated in cancer, here we have studied its function in breast cancer cell lines. Using human breast cancer cell lines, ZFAS1 was found to be expressed in all cell lines tested, albeit at different levels of abundance. Following subcellular fractionation, human ZFAS1 was found in both nucleus and cytoplasm (as is the mouse orthologue) in an isoform-independent manner. Sucrose gradients based on velocity sedimentation were utilised to separate the different components of total cell lysate, and surprisingly ZFAS1 was primarily co-localised with light polysomes. Further investigation into ribosome association through subunit dissociation studies showed that ZFAS1 was predominantly associated with the 40S small ribosomal subunit. The expression levels of ZFAS1 and of mRNAs encoding several ribosomal proteins that have roles in ribosome assembly, production and maturation were tightly correlated. ZFAS1 knockdown significantly reduced RPS6 phosphorylation. A large number of lncRNAs associate with ribosomes but the function of the majority of these lncRNAs has not been elucidated. The association of the lncRNA ZFAS1 with a subpopulation of ribosomes and the correlation with expression of mRNAs for ribosomal proteins suggest a ribosome-interacting mechanism pertaining to their assembly or biosynthetic activity. ZFAS1 may represent a new class of lncRNAs which associates with ribosomes to regulate their function. This article was reviewed by Christine Vande Velde, Nicola Aceto and Haruhiko Siomi.
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         lncRNA
         Ribosome
         Protein translation
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         Small subunit of ribosome
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