**Author details**

among the untranslated regions of the genome [61]. Intronic editing mediated by ADAR1 contributes to the maintenance of mature mRNA by protecting it against unfavorable processing of the Alu sequence and by degradation of aberrant transcripts by nonsense‐mediated decay (NMD) [42]. A‐to‐I RNA editing is diminished in brain tissue from patients with Alzheimerʹs disease relative to controls [62]. The reduction occurs predominantly in the hippocampus and to a lesser extent in the temporal and frontal lobes. These alterations result in decreased levels of protein recoding, the process of changing the amino acid sequence by A‐to‐I editing, in Alzheimerʹs disease [62]. The APOBEC3 family of cytidine deaminases has been associated with mutations in cancer genomes in several types of cancer. Accumulated data linking mutations in oncogenes and tumor suppressor genes with APOBEC3B activity are providing evidence that cytidine deaminase‐induced mutagenesis is activated in tumori-

Pseudo‐seq revealed that mRNA Ψ marks mRNA are regulated in response to stimuli, such as serum starvation in human cells and nutrient deprivation in yeast. The observations indicate that Ψ triggers a rapid regulatory mechanism to rewire the genetic code through inducible mRNA [16]. Pseudouridylation of rRNA and telomerase RNA component (TERC) were also found to be reduced in dyskeratosis congenita patients [17]. Furthermore, missense mutations in pseudouridine synthase 1 (PUS1) may lead to deficient pseudouridylation of mitochondrial tRNAs in mitochondrial myopathy and sideroblastic anemia (MLASA)

NAD captureSeq identified NAD as a 5ʹ RNA cap in a subset of regulatory RNAs in bacteria [43] and subsequently proposed that this type of capping may be common across all of life [65]. It is safe to predict that investigation of the roles and mechanisms of 5ʹ NAD caps in eukaryotes will draw increasing attention in the biomedical field. This is due to mainly two reasons. First, the chemical modification of the 5ʹ end of RNA is critical for RNA processing, localization, stability, translational efficiency, and epitranscriptomic regulation of gene expression [66]. Second, NAD is both a co‐substrate for enzymes, such as the sirtuins and poly(adenosine diphosphate‐ribose) polymerases, and a critical electron‐carrying coenzyme for enzymes that catalyze oxidation‐reduction reactions. NAD is involved in nearly all physiological processes.

levels are modulated during aging, and the use and production

usage has been associated with prolonged health and life spans [67]. Regulation of

NAD‐mediated RNA capping and hence gene expression will undoubtedly enrich our under-

Although rapid advances have been made in the past few years in epitranscriptomics, more work is needed in this field. To date, more than 140 different RNA modifications have been identified. However, there are only a few reliable high‐throughput techniques available to determine the global occurrence of a particular RNA modification. Thus, there is a need for the development of more high‐throughput techniques to characterize the full spectra of RNA modifications. It is also important to pursue the comprehensive

standing of NADʹs expanding roles in normal physiology and disease pathogenesis.

genesis, thus providing novel therapeutic targets [63].

286 Applications of RNA-Seq and Omics Strategies - From Microorganisms to Human Health

patients [64].

of NAD+

**5. Perspective**

For example, cellular NAD+

Min Xiong1 , Daniel P. Heruth1 , Xun Jiang<sup>2</sup> , Shamima Islam1 , Li Qin Zhang1 , Ding‐You Li<sup>3</sup> and Shui Q. Ye1,4\*

\*Address all correspondence to: sqye@cmh.edu

1 Division of Experimental and Translational Genetics, The Children's Mercy Hospital, MO, USA

2 Department of Pediatrics, Tangdu Hospital, Fourth Military Medical University, Xian, China

3 Division of Pediatric Gastroenterology, University of Missouri Kansas City School of Medicine, MO, USA

4 Department of Biomedical and Health Informatics, University of Missouri Kansas City School of Medicine, MO, USA
