Long INterspersed Element class 1 (LINE‐1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition‐competent LINE‐1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE‐1 repressors and when mutated cause the autoinflammatory disorder Aicardi‐Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE‐1 retrotransposition. It has therefore been suggested that increased LINE‐1 activity may be the cause of aberrant innate immune activation in AGS. Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE‐1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE‐1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE‐1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE‐1‐derived nucleic acids driving autoinflammation in AGS.

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Dietary nucleotides are required nutrients for some tissues under certain circumstances. A lack of dietary nucleotides negatively influences protein synthesis in both the liver and the small intestine of rats. Ribosome degradation has been observed as being among the mechanisms responsible for this effect. Dietary nucleotides can also modulate gene expression by interaction with specific transcription factors, in both the liver and the small intestine.Dietary nucleotides: Protein synthesis: Gene regulation IntroductionNucleotides are normal components of the human diet and the body provides mechanisms for their absorption and incorporation into tissues (for a review see Sánchez-Pozo et al. 1998). These compounds are not considered to be essential nutrients because they can be synthesized endogenously. In fact, no particular disease has been related to a nucleotide deficiency. However, in certain circumstances, and for some tissues, a lack of dietary nucleotides may impair important functions, suggesting a key nutritional role.Cellular proliferation, among other biological processes, requires significant amounts of nucleotides. Synthesis of nucleotides from amino acids and phosphoribosylpyrophosphate is an energy consuming process and therefore the utilization of exogenous nucleotides may be beneficial from a bioenergetic point of view. In the absence of exogenous nucleotides the de novo synthesis is thought to be activated (Yamaoka et al. 1997). Some tissues such as the lymphoid tissue (Perignon et al. 1987) or the intestine (Leleiko et al. 1983) have a low biosynthetic capacity, probably being dependent on an exogenous supply (Uauy, 1989;Van Buren & Rudolph, 1997).Dietary nucleotides may also be conditionally essential nutrients in a variety of clinical situations and during development. Thus, it has been shown that they accelerate the recovery of the liver and small intestine after a variety of insults (Núñez et al. 1990;Bueno et al. 1994;Uauy et al. 1994;Jackson et al. 1997;Torres et al. 1997;Tsujinaka et al. 1997;Yamamoto et al. 1997). They also promote maturation in both the liver and the small intestine (Uauy, 1989;Carver, 1994; Ortega et al. 1995a). Maturation of the small intestine is particularly important in neonates because of their rapid growth, especially in low-birth-weight infants due to their intrauterine malnutrition. Among other actions, dietary nucleotides have a significant effect in immunity (Carver, 1994;Yamamoto et al. 1997;Carver, 1999; Rueda & Gil, 2000). Therefore, nucleotide supplementation of formulas for infant nutrition or for parenteral nutrition is considered beneficial.The mechanisms by which dietary nucleotides exert their effects are not fully understood. However, there are data to suggest that they affect some biosynthetic processes such as the synthesis of proteins. Furthermore, there is evidence that they can modulate gene expression. Dietary nucleotides and biosynthetic processesWhen the rat diet does not contain nucleotides there is a transient decrease in the RNA conte...

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