Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.

There was an error published in J. Cell Sci. 121, 939-946.The reverse primer sequence for RT-PCR in the Materials and Methods is given in the 3¢-to-5¢ direction, not the 5¢-to-3¢ direction as stated. The correct sequence of the reverse primer is 5¢-TCTTGTGCCATGAGACTCCATCAG-3¢.The authors apologise for this error.

Introduction Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active genedependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel-BiskisReilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK).

There was an error published in J. Cell Sci. 121, 939-946.The reverse primer sequence for RT-PCR in the Materials and Methods is given in the 3¢-to-5¢ direction, not the 5¢-to-3¢ direction as stated. The correct sequence of the reverse primer is 5¢-TCTTGTGCCATGAGACTCCATCAG-3¢.The authors apologise for this error.

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