Apoptosis: the importance of being eaten

In vivo, cells undergoing apoptosis are usually recognised and swiftly ingested by macrophages or neighbouring cells acting as semi-professional phagocytes. This review debates evidence that the contents of apoptotic cells represent a danger to the organism, being capable of injuring tissue directly or triggering autoimmune responses, concluding that phagocytic clearance of intact apoptotic cells is a safe disposal route. Indeed, new data suggest that, in certain circumstances, phagocytes ingesting apoptotic cells may actively downregulate inflammatory and immune responses. Consequently, increasing evidence that there may be factors capable of perturbing safe clearance of apoptotic cells in vivo suggests that failure of this process may be a hitherto unrecognised pathogenetic factor in inflammatory and autoimmune diseases. New treatments designed to promote safe phagocytic clearance of dying cells can be anticipated, and it may even prove possible to eliminate unwanted cells by inducing appearance of cell surface 'eat me' signals.     

Eukaryotic evolution: the importance of being archaebacterial

Approximately half of all eukaryotic genes show signs of prokaryotic origin. Genes derived from eubacteria are more abundant than those from archaebacteria, but the latter are functionally more important. This supports archaebacteria as founding ancestors of the eukaryotic nucleus.     

Regulation of splicing: the importance of being translatable

RNA sequences that conform to the consensus sequence of 5' splice sites but are not used for splicing occur frequently in protein coding genes. Mutational analyses have shown that suppression of splicing at such latent sites may be dictated by the necessity to maintain an open reading frame in the mRNA. Here we show that stop codon frequency in introns having latent 5' splice sites is significantly greater than that of introns lacking such sites and significantly greater than the expected occurrence by chance alone. Both observations suggest the occurrence of a general mechanism that recognizes the mRNA reading frame in the context of pre-mRNA.     

On the importance of being finished

The publication of an increasing number of draft genome sequences presents problems that will only be resolved by improved search tools and by complete finishing of the sequences - and their deposition in publicly accessible databases.     

Activation induced deaminase: the importance of being specific

Activation-induced deaminase (AID) is required for class switch recombination and somatic hypermutation in immunoglobulin genes. Although the preponderance of evidence suggests that AID functions by deaminating deoxycytidine in DNA, the question remains whether it can also deaminate cytidine in mRNA, as originally proposed based on its homology to RNA-editing enzymes. Recently, the biological relevance of assaying mammalian enzymes for DNA deaminase activity using Escherichia coli DNA as a reporter has been questioned, representing another round in the ongoing debate.     

The importance of being dimeric

Why are there so many dimeric proteins and enzymes? While for heterodimers a functional explanation seems quite reasonable, the case of homodimers is more puzzling. The number of homodimers found in all living organisms is rapidly increasing. A thorough inspection of the structural data from the available literature and stability (measured from denaturation-renaturation experiments) allows one to suggest that homodimers can be divided into three main types according to their mass and the presence of a (relatively) stable monomeric intermediate in the folding-unfolding pathway. Among other explanations, we propose that an essential advantage for a protein being dimeric may be the proper and rapid assembly in the cellular milieu.     

The importance of being K-Ras

The ras genes give rise to a family of related proteins that have strong transforming potential. Typical in vitro studies fail to discriminate between the transforming activity of the Ras proteins. Although activating mutations in ras genes are commonly found in human disease, they are not evenly distributed between the different ras members. Instead, they are concentrated in k-ras. With the absence of evidence to suggest that k-ras DNA is more prone to mutation than h-ras DNA, this imbalance in mutational frequency suggests a special biological role for the K-Ras protein in vivo.