Simian hemorrhagic fever virus (SHFV) is a member of the family Arteriviridae. SHFV causes a highly acute and typically fatal diseases in Asian macaques. The genome of SHFV, like many RNA viruses, is expected to possess RNA structural elements that regulate key steps in the virus life cycle. However, these structural elements are largely unknow and remain uncharacterized. We investigated potential regulatory RNA structures encoded with the SHFV genome. Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) analysis revealed two prominent 5′ structures: a four-arm cloverleaf-like fold in the 5′ untranslated region (5′ UTR) and a worm-like structure in the nsp1β coding sequences. By mutational analyses, we investigated their role in viral translation and replication. The cloverleaf structure was found to be essential for both translation and replication. The B-arm of the cloverleaf was revealed to be critical for efficient translation. Maintaining the overall structure of the cloverleaf, specifically, the A, B, and C arms were necessary for viral RNA synthesis and virion production. In contrast, the alteration of the worm structure showed minimal impact on viral replication, though it may influence the expression of the nsp1β protein. Also, the worm structure harbors a repeating unit that could potentially be important for genome encapsidation. These findings demonstrated that 5′ RNA elements in the SHFV genome regulate translation, replication, and virus yield. This study highlights the importance of RNA structural elements in the SHFV genome. In addition, we investigated two microproteins (MP86 and MP73) encoded in the SHFV genome. Both proteins were predicted to fold into a helix-loop-helix structure with MP73 and MP86 containing one and two transmembrane domains, respectively. Co-immunoprecipitation coupled with mass spectrometry in SHFV infected cells revealed numerous protein associations with MP86 and fewer proteins with MP73. Many of the cellular proteins identified with the MP86 participate in transport and are ER-associated, whereas, those identified with MP73 are linked to caveola assembly and mitochondria. In support of this finding, immunofluorescence analysis revealed that MP86 and MP73 localizes to the ER and mitochondria respectively. The data provided an initial foundation for understanding the functions of these microproteins in SHFV infection.