Molecular Biology Select

Progress toward understanding the function and regulation of noncoding RNAs is the topic of this issue's Molecular Biology Select. Recent reports provide mechanistic insight into the regulation of transcription by noncoding RNAs found at gene promoters. Other findings reveal a new mechanism for the regulation of attenuated noncoding transcripts, provide evidence for the involvement an antisense transcript in Alzheimer's disease, and shed light on the evolutionary conservation of imprinting mechanisms in mammals. Cyclin D1 is a cell cycle regulator that is repressed by DNA damage to prevent cell cycle progression while DNA lesions are being repaired. Wang et al. (2008) have recently shown that DNA damage signals enhance the expression of noncoding RNAs that are tethered to the 5 0 regulatory region of the cyclin D1 gene. These noncoding RNAs recruit the RNA binding protein translocated in liposarcoma (TLS), which in turn binds and inhibits the histone acetyltransferases CREB-binding protein (CBP) and p300. The resulting suppression of local histone acetylation inhibits cyclin D1 transcription. Remarkably, this entire process is RNA dependent, indicating that the noncoding RNA is an allosteric regulator of TLS. These findings reveal a new means by which transcription can be regulated in response to cellular signals and a new function for non-coding RNAs. Future efforts will determine the chain of signals that link DNA damage to the expression of the noncoding RNAs and may reveal whether noncoding RNAs are expressed in the 5 0 regulatory regions of other genes whose expression is repressed by DNA damage signals. For some genes, the selection of the start site of transcription is an important feature of their regulation, with some start sites leading to attenuated transcripts that are targeted for degradation. Kuehner and Brow (2008) now show that the concentration of nucleotides can regulate which transcription start site is selected by RNA polymerase II (pol II). Although the potential functional consequences of this type of regulation are numerous, the example provided by the authors is a compelling one.They studied transcription of the yeast gene inosine monophosphate dehydrogenase 2 (IMD2), which encodes a key enzyme in guanosine triphosphate (GTP) biosynthesis. They observe that when the GTP concentration is high, upstream guanines are favored as the start sites for transcription. This leads to the production of attenuated noncoding transcripts because of the presence of a terminator sequence recognized by the helicase Sen-1 via its associated RNA-binding proteins. When GTP levels are low, …