Identification and characterization of the role of noncoding RNA for gene regulation of metabolic processes in cattle

对于不同细胞和组织类型和表型的基因表达的调节，不同的染色质结构以及DNA与蛋白质和非编码RNA(NcRNA)的相互作用是重要的。自从下一代全球RNA测序技术(RNAseq)被引入以来，在人类和模型动物的转录本中发现的非编码转录本的数量正在迅速增加。大量研究表明，除短非编码RNA外，长非编码RNA(LnRNAs)也是相关分子调控过程中的重要功能成分，与特定的分化和生长过程有关，并与多种疾病的发病有关。根据目前对其他物种中LncRNAs功能相关性的了解，我们推测这些非编码转录本也可能在牛不同表型的复杂代谢模式的调节中发挥调节作用。本项目的目的是确定调控性状分化牛代谢和能量分配的lncRNAs和lncRNAs相关机制，以调控牛的能量和饲料转化效率以及不同代谢类型的不同遗传-生理构成。与注释良好的人和小鼠的转录组相比，牛的转录组仍然没有得到充分的注释和识别。为了建立全面的转录组目录，我们将使用全球转录组测序的无假设方法来识别和注释来自奶牛类型x肉牛型杂交群体中与代谢相关的组织的未知和非编码转录物。一些可能针对代谢类型的差异表达的LncRNAs将被选择用于全基因组范围内使用ChIRPseq(染色质分离RNA纯化测序)的方法来鉴定和定位LncRNA相互作用的DNA区域。作为该研究的结果，我们期待对牛基因组和转录组进行更深层次的功能注释。此外，我们想要阐明，lncRNAs是否以及在多大程度上代表中央调控节点，在那里可以感受到能量代谢的变化，并特异性地调节适应性基因的表达。表达谱和新的功能基因信息有助于阐明和提高我们对不同代谢过程调控的分子理解。此外，代谢类型特定的表达特征可用于开发针对特定表型的分子生物标志物，以便基于对相应代谢类型的特定调控过程的了解，为牛的选择和管理提供改进的方法。

For the regulation of gene expression in different cell and tissue types and phenotypes different chromatin architecture as well as DNA interactions with proteins and noncoding RNAs (ncRNA) are important. Since the global RNA sequencing technology of the next generation (RNAseq) has been introduced the number of noncoding transcripts discovered in the transcriptomes of human and model animals is rapidly increasing. Numerous studies showed that besides the short noncoding RNAs, the long noncoding RNAs (lnRNAs) are also an important functional component involved in relevant molecular regulatory processes and associated with specific differentiation and growth processes and with the pathogenesis of a variety of diseases. Based on current knowledge regarding functional relevance of lncRNAs in other species we postulate that these noncoding transcripts may also play a regulatory role in the modulation of complex metabolic pattern characterizing different phenotypes in cattle. The aim of this project is to identify lncRNAs and lncRNAs-associated mechanisms that regulate metabolism and energy partitioning of trait-differentiated cattle, which may modulate efficiency of energy and feed transformation and the different genetic-physiological make-up of divergent metabolic types in cattle. Compared to the well annotated transcriptomes of human and mouse the bovine transcriptome is still inadequately annotated and insufficiently identified. To establish comprehensive transcriptome catalogs we will use the hypothesis-free approach of global transcriptome sequencing to identify and annotate yet unknown and noncoding transcripts from metabolically relevant tissues of trait-differentiated cattle from a dairy type x beef type cross population. Some of the differentially expressed lncRNAs, which are potentially specific for metabolic types, will be selected for genomewide identifying and mapping of lncRNA-interacting DNA-regions using the method of ChIRPseq (Chromatin Isolation by RNA Purification Sequencing).As a result of the study we expect a deeper functional annotation of the bovine genome and transcriptome. Moreover, we want to elucidate, whether and to what extent lncRNAs represent central regulatory nodes, where changes in energy metabolism can be sensed and adaptive gene expression is modulated specifically. The expression profiles and novel functional gene information can contribute to clarify and improve our molecular understanding regarding the regulation of divergent metabolic processes. In addition, metabolic type-specific expression signatures can be used to develop molecular biomarkers for defined phenotypes in order to provide improved methods for selection and management of cattle based on knowledge of specific regulatory processes in the respective metabolic type.