Genomic studies have revealed that humans possess far fewer protein-encoding 
genes than originally predicted. These over-estimates were drawn from the 
inherent developmental and stimuli-responsive complexity found in humans and 
other mammals, when compared to lower eukaryotic organisms. This left a 
conceptual void in many cellular networks, as a new class of functional 
molecules was necessary for "fine-tuning" the basic proteomic machinery. 
Transcriptomics analyses have determined that the vast majority of the genetic 
material is transcribed as noncoding RNA, suggesting that these molecules could 
provide the functional diversity initially sought from proteins. Indeed, as 
discussed in this review, long noncoding RNAs (lncRNAs), the largest family of 
noncoding transcripts, have emerged as common regulators of many cellular 
stressors; including heat shock, metabolic deprivation and DNA damage. These 
stimuli, while divergent in nature, share some common stress-responsive 
pathways, notably inhibition of cell proliferation. This role intrinsically 
makes stress-responsive lncRNA regulators potential tumor suppressor or 
proto-oncogenic genes. As the list of functional RNA molecules continues to 
rapidly expand it is becoming increasingly clear that the significance and 
functionality of this family may someday rival that of proteins. This article is 
part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited 
by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.